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Background: Plasmonic core-shell nanostructures with embedded internal markers used as Raman probes have attracted great attention in surface-enhanced Raman scattering (SERS) immunoassay for cancer biomarkers due to their excellent uniform enhancement. However, current core-shell nanostructures typically exhibit a spherical shape and are coated with a gold shell, resulting in constrained local field enhancement., Results: In this work, we prepared a core-shell AuNR@BDT@Ag structure by depositing silver on the surface of Raman reporter-modified gold nanorods (AuNR). With cysteamine-driven specific deposition of Ag atoms, the internal standard nanoprobes with an ortho-tetrahedral morphology were obtained. Owing to its tetrahedral morphology and the effective plasmon coupling at the Ag-Au interface, this internal standard Raman probe exhibited excellent Raman enhancement. Also, with embedded Raman reporter, the probes of Au nanorod in Ag tetrahedron avoided the desorption of Raman reporter and competitive adsorption of interfering molecule, which greatly improved the stability and reproducibility of SERS signal and addressed the drawbacks of low reproducibility existing in SERS immunoassay. The feasibility of the AuNR@BDT@Ag probe was demonstrated by the sensitive detection of the liver cancer biomarker alpha-fetoprotein (AFP) in Eppendorf (EP) tubes and microfluidic chips. The results in EP tubes revealed a linear range of 1 fg/mL-1 ng/mL and a detection limit of 0.631 fg/mL. When the detection was performed in microfluidic chips, the linear range was 10 pg/mL to 0.1 μg/mL, with a limit detection of 8.29 pg/mL., Significance: The performance of AFP detection in EP tubes and microfluidic chips demonstrates that the tetrahedral core-shell AuNR@BDT@Ag nanostructures used as internal standard Raman probes have the potential to detect biomarkers in blood samples for cancer screening., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 Elsevier B.V. All rights reserved.)

Objective: This study aims to assess the predictive value of serum lipoprotein-associated phospholipase A2 (Lp-PLA2) in colorectal liver metastasis (CRLM) patients., Methods: A total of 507 participants were recruited for this study, comprising 162 healthy controls (HCs), 186 non-CRLM patients, and 159 CRLM patients. Serum Lp-PLA2 levels were measured across these three groups, and a CRLM prediction model was developed using machine learning (ML) algorithms in conjunction with traditional serological markers. The performance of each model was assessed using the area under the receiver operating characteristic (ROC) curve (AUC), sensitivity, specificity, and other relevant metrics., Results: The serum Lp-PLA2 levels in CRLM patients were significantly elevated compared to those in HCs group and the non-CRLM group (P < 0.0001). The CRLM prediction model developed using the Random forest algorithm demonstrated superior performance, incorporating six features: Lp-PLA2, ALB, GLB, ALT, LDH, and TC. This model achieved an AUC of 0.918, with a sensitivity of 0.823, specificity of 0.889, positive predictive value (PPV) of 0.861, and negative predictive value (NPV) of 0.857., Conclusion: The Random forest model, incorporating serum Lp-PLA2 level and conventional laboratory parameters, demonstrates robust predictive capability for CRLM and holds promise for enhancing early detection in CRLM patients., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 The Author(s). Published by Elsevier B.V. All rights reserved.)

Introduction: Higher concentrations of the small-cell lung cancer (SCLC) serum marker, pro-gastrin-releasing peptide (proGRP), in lung inflammations has been indicated in literature. The objective of this study was to compare serum proGRP concentration in pneumonia, chronic obstructive pulmonary disease (COPD) and early-stage primary lung cancers., Materials and Methods: An observational study was performed to assess serum proGRP against other lung cancer markers in pneumonia, COPD and in stage 1/2 carcinomas. A total of 91 cases of pneumonia or chronic obstructive pulmonary disease (COPD), with 107 cases of early-stage lung adenocarcinoma (ADC), squamous cell carcinoma (SQCC) and 14 cases of neuroendocrine tumors (NET), including SCLC, were analyzed. Serum proGRP (Roche Diagnostics, Basel, Switzerland), cytokeratin 19 fragment 21-1, carcinoembryonic antigen, neuron-specific enolase and C-reactive protein were measured and compared. For the statistical analysis, Mann-Whitney U test, Kruskal-Wallis ANOVA, multiple linear and multinomial logistic regression modeling were used., Results: Compared to the early-stage ADC and SQCC, proGRP in pneumonia, COPD and in NET was higher (P ≤ 0.011 in all comparisons). In 11 cases of pneumonia and COPD, proGRP reached cut-off for SCLC of 100 ng/L. No clinically relevant differences between pneumonia or COPD and early-stage cancer were observed for other markers. Concentration of proGRP was associated with CRP (model coefficient was 0.20; P < 0.019) and both parameters contributed to classification of cases to pneumonia/COPD, ADC/SQCC, and NET categories (P < 0.004, in all cases)., Conclusions: Concentrations of proGRP in pneumonia and COPD patients were higher than in patients in the ADC and SQCC early stages and could exceed the SCLC cut-off., Competing Interests: Potential conflict of interest None declared., (Croatian Society of Medical Biochemistry and Laboratory Medicine.)

Transformation of epithelial to mesenchymal (EMT) is an important event in the process of tumor initiation, invasion and metastasis. Circulating tumor cells (CTCs) are one kind of important markers in the field of liquid tumor biopsy, whose number and phenotype represent the occurrence and progression of tumors. Therefore, it is our interest to investigate the epithelial mesenchymal transition process occurring on the surface of CTCs. Herein in this work, two proteins of E-cadherin (E-cad) and N-cadherin (N-cad) were selected as representative proteins of EMT process. To achieve simultaneous analysis of E-cad and N-cad on the surface of rare CTCs, we designed a duplex and portable immunosensor using AuNPs and AgNPs as nanolabels to amplify the immunoreaction signals. The dual channel immunosensor not only exhibited good electrochemical responses for recombinant E-cad and N-cad as low as 0.1 ng/mL and 0.05 ng/mL, respectively, but also showed good linear correlations with different numbers of phenotypic CTCs (10-500 cells/10 μL). The above strategy was further employed to inspect the occurrence of EMT on CTCs surface, which displayed a high consistence with other molecular biological characterizations. Finally, this immunoassay was successfully applied to inspect the correlations of numbers, phenotype of CTCs, as well as E-cad and N-cad expressions on these CTCs in bloods of NSCLC patients with disease stage., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Local recurrence after radiotherapy is common in locally advanced head and neck cancer (HNC) patients. Re-irradiation can improve local disease control, but disease progression remains frequent. Hence, predictive biomarkers are needed to adapt treatment intensity to the patient's individual risk. We quantified circulating tumor DNA (ctDNA) in sequential plasma samples and correlated ctDNA levels with disease outcome. Ninety four longitudinal plasma samples from 16 locally advanced HNC patients and 57 healthy donors were collected at re-radiotherapy baseline, after 5 and 10 radiation fractions, at irradiation end, and at routine follow-up visits. Plasma DNA was subjected to low coverage whole genome sequencing for copy number variation (CNV) profiling to quantify ctDNA burden. CNV-based ctDNA burden was detected in 8/16 patients and 25/94 plasma samples. Ten additional ctDNA-positive samples were identified by tracking patient-specific CNVs found in earlier sequential plasma samples. ctDNA-positivity after 5 and 10 radiation fractions (both: log-rank, p = .050) as well as at the end of irradiation correlated with short progression-free survival (log-rank, p = .006). Moreover, a pronounced decrease of ctDNA toward re-radiotherapy termination was associated with worse treatment outcome (log-rank, p = .005). Dynamic ctDNA tracking in serial plasma beyond re-radiotherapy reflected treatment response and imminent disease progression. In five patients, molecular progression was detected prior to tumor progression based on clinical imaging. Our findings emphasize that quantifying ctDNA during re-radiotherapy may contribute to disease monitoring and personalization of adjuvant treatment, follow-up intervals, and dose prescription., (© 2024 The Author(s). International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

The mannose receptor (MR/CD206) is a marker of M2-like tumor-associated macrophages. Membrane CD206 can be shed, releasing the receptor as a soluble protein (sCD206), which can be measured in serum. Here, we investigated the biomarker potential of sCD206 in patients with metastatic renal cell carcinoma (mRCC). Serum sCD206 was measured by an enzyme-linked immunosorbent assay in 88 mRCC patients and 20 healthy controls (HCs). At diagnosis, serum sCD206 was elevated in patients with intermediate-risk mRCC according to the Memorial Sloan Kettering Cancer Center (MSKCC) risk score, compared to both HCs and patients with favorable MSKCC risk score. Furthermore, sCD206 levels correlated with both sCD163 and C-reactive protein. Soluble CD206 levels decreased after treatment initiation (p < .0001 at 5 weeks) but with a tendency toward elevated levels at time of progression, compared to baseline (p = .06). In univariate survival analysis, high levels of serum sCD206 at baseline was a significant risk factor associated with reduced overall survival (hazard ratio [HR] = 1.37, 95% confidence interval: 1.12-1.67, p = .002). Stratified by clinical risk scores, increased sCD206 was still a statistically significant risk factor of overall mortality (p < .01) in the intermediate-risk group by both the MSKCC (HR = 1.48) and the newer International Metastatic RCC Database Consortium (IMDC) score (HR = 1.53). Furthermore, addition of sCD206 as a dichotomized variable to the IMDC risk score enabled separation of the intermediate-risk group into two groups with survival comparable to those with favorable and poor risk, respectively. Overall, sCD206 is a potential add-on biomarker for mRCC patients in the intermediate-risk group of the current clinical risk scores., (© 2024 The Author(s). International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

Screening plays a crucial role in the early detection of colorectal cancer, greatly reducing mortality rates. The objective of this study was to identify a non-invasive diagnostic method utilizing serum microRNA expression for the diagnosis of colorectal cancer patients. The study consisted of three stages. In the first stage, 129 patients with colorectal cancer and 129 normal subjects were recruited as the training set for the development of a blood miRNA panel. The second stage involved recruiting 200 patients from each group as the validation cohort. Finally, a blinded study was conducted in the third stage, with 260 patients recruited to determine the predictive value of our miRNA panel. Serum samples were prospectively collected from colorectal cancer patients and normal subjects between 2017 and 2021 at Queen Mary Hospital in Hong Kong. Quantitative PCR was utilized to detect the serum levels of candidate microRNAs, and a multiple linear regression model was employed to formulate a serum microRNA panel for diagnosing colorectal cancer patients. The performance of the panel was evaluated using ROC analysis. Our study showed that the values of three pairs of serum microRNAs, namely miR-106b-5p/miR-1246, miR-106b-5p/miR-16 and miR-106b-5p/miR-21-5p, exhibited statistically significant differences between colorectal cancer patients and normal subjects. A serum microRNA panel formulated from these three pairs of microRNAs demonstrated high accuracy in diagnosing colorectal cancer patients from normal subjects, with an AUC of approximately 0.9. The serum miRNA test proved to be a feasible and promising non-invasive biomarker for the diagnosis of colorectal cancer patients in comparison to normal subjects., (© 2024 The Author(s). International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

Extracellular vesicles (EVs) and EV-derived microRNAs (EV-miRNAs) are emerging as promising circulating biomarkers for early detection of malignant tumors such as non-small cell lung cancer (NSCLC). However, utilization of the gold standard method of RNA detection, the reverse transcription - quantitative polymerase chain reaction (RT-qPCR), on EV-miRNAs is hindered by laborious sample purification requirements and time-consuming multi-step procedures. Herein, we propose and demonstrate a miniaturized digital microfluidic (DMF) workstation for all-in-one EV-miRNA detection based on RT-qPCR. In comparison with the previously reported DMF platform for EV isolation, the system further integrates parallel on-chip real-time PCR capability with a comparable detection sensitivity with in-vitro RT-qPCR (limit of detection = 2 copies/μL), realizing automated, miniaturized, and facile EV-miRNA detection. Meanwhile, major methodological improvements were made, including one-step stem-looped RT-qPCR for miRNAs with both high sensitivity and specificity, and a simplified DMF substrate rework strategy for cost-effectiveness. As a demonstration, the detection of NSCLC-related EV-miRNAs within 20 μL of plasma samples was implemented, indicating the potential applicability of the DMF workstation and its automated protocol on point-of-care diagnosis of a wide range of diseases., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Prostate cancer represents the second most prevalent form of cancer in males globally. In the diagnosis of prostate cancer, the most commonly utilised biomarker is prostate-specific antigen (PSA). It is unfortunate that approximately 25 % of men with elevated PSA levels do not have cancer, and that approximately 20 % of patients with prostate cancer have normal serum PSA levels. Accordingly, a more sensitive methodology must still be identified. It is imperative that new diagnostic methods should be non-invasive, cost-effective, rapid, and highly sensitive. Fourier transform infrared spectroscopy (FTIR) is a technique that fulfils all of the aforementioned criteria. Consequently, the present study used FTIR to assess dried serum samples obtained from a cohort of prostate cancer patients (n = 53) and a control group of healthy individuals (n = 40). Furthermore, this study proposes FTIR markers of prostate cancer obtained from serum. For this purpose, FTIR spectra of dried serum were measured and analysed using statistical, chemometric and machine learning (ML) algorithms including decision trees C5.0, Random Forest (RF), k-Nearest Neighbours (kNN) and Support Vector Machine (SVM). The FTIR spectra of serum collected from patients suffering from prostate cancer exhibited a reduced absorbance values of peaks derived from phospholipids, amides, and lipids. However, these differences were not statistically significant. Furthermore, principal component analysis (PCA) demonstrated that it is challenging to distinguish serum samples from healthy and non-healthy patients. The ML algorithms demonstrated that FTIR was capable of differentiating serum collected from both analysed groups of patients with high accuracy (values between 0.74 and 0.93 for the range from 800 cm -1 to 1800 cm -1 and around 0.70 and 1 for the range from 2800 cm -1 to 3000 cm -1 ), depending on the ML algorithms used. The results demonstrated that the peaks at 1637 cm -1 and 2851 cm -1 could serve as a FTIR marker for prostate cancer in serum samples. Furthermore, the correlation test indicated a clear correlation between these two wavenumbers and four of the five clinical parameters associated with prostate cancer. However, the relatively small number of samples collected only from patients over the age of 60 indicated that the results should be further investigated using a larger number of serum samples collected from a mean age range. In conclusion, this study demonstrated the potential of FTIR for the detection of prostate cancer in serum samples, highlighting the presence of distinctive spectroscopic markers associated with the analysed cancer type., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Predicting cancer-associated clinical events is challenging in oncology. In Multiple Myeloma (MM), a cancer of plasma cells, disease progression is determined by changes in biomarkers, such as serum concentration of the paraprotein secreted by plasma cells (M-protein). Therefore, the time-dependent behavior of M-protein and the transition across lines of therapy (LoT), which may be a consequence of disease progression, should be accounted for in statistical models to predict relevant clinical outcomes. Furthermore, it is important to understand the contribution of the patterns of longitudinal biomarkers, upon each LoT initiation, to time-to-death or time-to-next-LoT. Motivated by these challenges, we propose a Bayesian joint model for trajectories of multiple longitudinal biomarkers, such as M-protein, and the competing risks of death and transition to the next LoT. Additionally, we explore two estimation approaches for our joint model: simultaneous estimation of all parameters (joint estimation) and sequential estimation of parameters using a corrected two-stage strategy aiming to reduce computational time. Our proposed model and estimation methods are applied to a retrospective cohort study from a real-world database of patients diagnosed with MM in the US from January 2015 to February 2022. We split the data into training and test sets in order to validate the joint model using both estimation approaches and make dynamic predictions of times until clinical events of interest, informed by longitudinally measured biomarkers and baseline variables available up to the time of prediction., (© 2025 The Author(s). Statistics in Medicine published by John Wiley & Sons Ltd.)

A shift toward a T cell exhaustion phenotype is associated with the upregulation of expression of programmed cell death protein 1 (PD-1) on T lymphocytes in patients with malignant solid tumors. The interaction between PD-1 and programmed death-ligand 1 (PD-L1) inhibits PD-1 + T lymphocyte function, impacting their anti-tumor immune activity. Immune checkpoint inhibitors targeting PD-1/PD-L1 have revolutionized the treatment of various solid malignancies, improving therapeutic efficacy and survival outcomes. Peripheral blood analysis of liquid biopsies is being increasingly used to identify populations most likely to benefit from various treatment modalities. PD-1 + T lymphocytes represent the primary cell population responsive to immunotherapeutic interventions for patients with solid malignancies, as evidenced by the altered PD-1 expression levels and proportion of cells comprising the overall population of immunocytes. PD-1 + T cells in peripheral blood exert an associative and reciprocal predictive effect on homologous intratumoral cells. Distinct subpopulations of PD-1 +  T cells exhibit differential ability to proliferate in the periphery and can be characterized by tumor antigen-specific and exhaustion phenotypes. These characteristics have prognostic implications, aiding in the prediction of the efficacy of antitumor therapy and predicting survival outcomes. We highlight distinct subpopulations of PD-1 +  T cells, their exhaustion and antigen-specific phenotypes, and their dynamic changes over treatment, providing insights into their utility for tailoring personalized therapies. For the first time, this review discusses the role of peripheral PD-1 +  T lymphocytes as prognostic biomarkers in liquid biopsies, focusing on their clinical significance, predictive value during therapy, and future research directions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Among cancer patients, pancreatic cancer patients have the highest rate of sarcopenia, which is a critical prognostic factor. Serum creatine kinase (CK) is closely related to skeletal muscle mass and has been reported to decline with the progression of cancer. This study investigated whether preoperative serum CK is associated with the survival of patients with pancreatic cancer., Methods: Data were obtained from patients with pathologically confirmed pancreatic cancer between June 2016 and March 2022. The prognostic significance of CK was analyzed based on sex-stratified groups. The Kaplan-Meier method was used to compare overall survival (OS) and disease-free survival (DFS). Multivariate Cox proportional hazards models were used to determine prognostic factors. Body composition was analyzed based on preoperative abdominal CT images to explore the sex-specific associations between skeletal muscle area (SMA) and serum CK levels., Results: A total of 166 patients were included in this study. Sarcopenia was presented in 70 patients (42.2%). A low serum CK level showed a significant correlation with the diagnosis of sarcopenia in male patients (P = 0.026). The levels of CK did not predict the outcome in female patients, while a low preoperative CK was notably linked to shorter OS in male patients (median OS: 15 months vs. 33 months, P = 0.011; median DFS: 5 months vs. 14 months, P = 0.007). Multivariate analyses further confirmed the effect of CK in predicting OS (CK>44 IU/L, HR:0.226, 95% CI:0.107-0.478, P < 0.001) and DFS (CK>44 IU/L, HR:0.272, 95% CI:0.139-0.529, P < 0.001) of male patients. Correlation analysis revealed a significant association between SMA and CK levels in male patients (r = 0.225, P = 0.025), and such a correlation was not observed in female patients (r = 0.088, P = 0.478)., Conclusion: The pretherapeutic CK may represent a simple marker for predicting poor survival in male patients with resectable pancreatic cancer, thereby aiding in the selection of therapeutic strategies., Competing Interests: Declarations. Ethics approval and consent to participate: This study was approved by the Ethics Committee of Fujian Medical University Union Hospital (Approval No.2023KY080). Informed consent was obtained from all individual participants included in the study. All methods of this study were carried out in accordance with relevant guidelines and regulations. Foundation: This work was supported by the National Natural Science Foundation of China (Grant No.: 82073139), the Natural Science Foundation of Fujian Province, China (No. 2020J02054), the Joint Funds for the Innovation of Science and Technology, Fujian Province (Grant number: 2021Y9058) and the Medical Minimally Invasive Center Program of Fujian Province and National Key Clinical Specialty Discipline Construction Program, China. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Background/aim: Cholinesterase (ChE) is important for estimating nutritional status and can be easily measured. This study aimed to investigate the effect of ChE on the short- and long-term prognoses of elderly patients with colorectal cancer., Patients and Methods: This study included 120 elderly patients who underwent scheduled surgery for colorectal cancer. ChE is a biomarker that can be easily measured using blood tests. The optimal cut-off level of ChE was determined using receiver operating characteristic analysis. We investigated the relationship of ChE with disease-free and overall survival using univariate and multivariate analyses., Results: Seventy-two (60%) patients had low ChE levels (<255 U/l). In the multivariate analysis, low ChE (p=0.04) was an independent and significant predictor of postoperative complications. Low ChE (p=0.049), low prognostic nutritional index (p=0.04), and lymph node metastasis (p<0.01) were independent and significant prognostic predictors of poor disease-free survival. American Society of Anesthesiologists Physical Status 3 (p<0.01), low ChE (p<0.01), and lymph node metastasis (p<0.01) were independent and significant predictors of poor overall survival., Conclusion: ChE level is a significant predictor of short- and long-term outcomes in elderly patients undergoing scheduled surgery for colorectal cancer., (Copyright © 2025 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Introduction: Immune check-point inhibitors (ICI) were a major breakthrough in cancer care, but optimal patient selection remains elusive in most tumors., Methods: Overall 173 adult patients with metastatic solid tumors candidates to ICI in clinical trials at our Institution were prospectively recruited. Blood samples were collected at cycle 1 (C1D1) and 2 (C2D1) and until the occurrence of progressive disease (PD). C1D1 LIPI, RMH, PMHI, NLR, dNLR, PIPO and GRIm prognostic scores were calculated. The primary endpoint was identifying the best score to predict rapid PD (≤ 4 months) with ICI using logistic regressions accounting for tumor type, and receiving operators characteristics (ROC) with area under curve (AUC), accompanied by an extensive comparison of the score performances in the prediction of overall survival (OS), progression-free survival (PFS), overall response rates (ORR) and durable clinical benefit (DCB). Secondary objectives included describing study cohort outcomes and studying the association between the selected score at C1D1, C2D1 and its dynamics with OS and PFS., Results: C1D1 LIPI was the best predictor of rapid PD, OS and PFS, regardless of cancer type, compared to other scores. No score was associated to ORR and only RMH to DCB. Baseline LIPI detected three categories of patients with significantly different OS (p < 0.001) and PFS (p = 0.013). The same was observed at C2D1 for OS and PFS (both p = 0.020). Significant LIPI class shifts were observed in the overall population (p < 0.001), rapid progressors (p = 0.029) and non-rapid progressors (p = 0.009). Retaining a good LIPI or experiencing a shift towards a better prognostic class was associated to improved OS (p = 0.009) and PFS (p = 0.006). C2D1 LIPI, but not C1D1, remained significantly associated to rapid PD in multivariable analysis., Conclusions: LIPI may improve patient selection for ICI and guide treatment adjustments according to on-treatment dynamics in a pancancer context., Competing Interests: Declarations. Conflict of interest: J. García-Corbacho reports travel expenses from BMS and Pfizer and honoraria from Astra Zeneca, GSK, Lilly, Regeneron, Roche and Pfizer. L. Mezquita reports grants/research support from Amgen, Inivata, AstraZeneca and Gilead, honoraria/consultation fees from Roche, Takeda, Janssen and MSD, lectures and educational activities for Bristol-Meyers Squibb, Roche, Takeda, AstraZeneca, MSD, Radonova and Janssen, travel accommodation/expenses from Bristol-Meyers Squibb, Roche, Takeda, AstraZeneca and Janssen. F. Brasó-Maristany reports patent application (PCT/EP2022/086493, PCT/EP2023/060810, EP23382703 and EP23383369). N. Basté participated in advisory boards for Nanobiotix, Merck Serono, MSD, BioNtech, Roche, and BMS. T. Saurí served as a consultant at AstraZeneca, BMS, Roche, MSD, AMGEN, and Daiichi Sankyo and received lecture fees from BMS and MSD; B. Mellado reports research funding from Janssen, Roche, Bayer, and Pfizer; speakers’ bureau for Roche, Sanofi, Janssen, Astellas, Pfizer, Novartis, and Bristol-Myers Squibb; and travel and accommodation expenses from Janssen and Pfizer. Ò. Reig reports consulting or advisory role for BMS, EISAI, and Ipsen; and travel and accommodation expenses from Ipsen and Pfizer. L. Gaba reports advisory and consulting fees from GlaxoSmithKline, AstraZeneca, Merk Sharp Dohme, and PharmaMar, honoraria from GlaxoSmithKline, AstraZeneca, Merk Sharp Dohme, and PharmaMar for educational events/materials and travel expenses from GlaxoSmithKline, AstraZeneca, Merk Sharp Dohme. A. Prat reports advisory and consulting fees from AstraZeneca, Roche, Pfizer, Novartis, Daiichi Sankyo, and Peptomyc, lecture fees from AstraZeneca, Roche, Novartis, and Daiichi Sankyo, institutional financial interests from AstraZeneca, Novartis, Roche, and Daiichi Sankyo; stockholder and employee of Reveal Genomics; patents filed PCT/EP2016/080056, PCT/EP2022/086493, PCT/EP2023/060810, EP23382703 and EP23383369. F. Schettini reports honoraria from Novartis, Gilead, Veracyte and Daiichy-Sankyo for educational events/materials, advisory fees from Pfizer and Veracyte, and travel expenses from Novartis, Gilead and Daiichy-Sankyo. The other authors report no conflict of interest. Ethics approval and consent to participate: The study protocol was approved by the Ethic Committee of the HCB (IRB n. HCB/2017/0371) and was conducted according to the Declaration of Helsinki, good clinical practice guidelines and in compliance with applicable national and local laws. All patients signed an informed consent before entering the study., (© 2025. The Author(s).)

Aim: The objective of this study was to investigate the prognostic significance of the preoperative serum albumin-bilirubin (ALBI) score in patients with colorectal cancer (CRC)., Methods: Preoperative ALBI data from 1506 CRC patients were categorized into high-value and low-value groups, and the clinicopathological characteristics of these groups were compared. A Cox proportional hazards regression model was employed to investigate the risk factors associated with distant metastasis. The Kaplan-Meier method and log-rank test were utilized to analyze the relationship between ALBI scores and 5-year distant metastasis-free survival (DMFS)., Results: The incidence of distant metastasis in group B (ALBI ≥ -2.4) was significantly higher at 28.81% compared to group A (ALBI < -2.4), which had an incidence of 23.36% ( p  = 0.018). ALBI score ≥ -2.4 was identified as an independent risk factor for postoperative distant metastasis of CRC (HR = 1.251, 95%CI: 1.021-1.533, p  = 0.031). The incidence of 5-year DMFS was significantly lower in the ALBI ≥ -2.4 group compared to that observed in the ALBI < -2.4 group (χ 2  = 5.97, p  = 0.015, log-rank test)., Conclusion: The ALBI score of ≥ -2.4 emerges as an independent risk factor for the occurrence of distant metastases following CRC surgery.

Background: Bilirubin has anti-inflammatory, antioxidant, and anti-cancer properties, with an inverse relationship between its levels and cancer risk and prognosis. However, the prognostic value of serum bilirubin in acute myeloid leukemia (AML) remains uncertain., Methods: This retrospective study analyzed pretreatment serum total bilirubin (TBIL), direct bilirubin (DBIL), and indirect bilirubin (IBIL) in 284 AML patients and 316 healthy controls. The prognostic significance of serum bilirubin levels was determined using the Kaplan-Meier method and Cox proportional hazards model., Results: Pretreatment TBIL and IBIL levels were significantly lower in AML patients compared to controls. TBIL and IBIL levels were significantly higher in the CR/CRh/CRi group than in the non-CR/CRh/CRi group and increased significantly after chemotherapy. Elevated pretreatment TBIL and IBIL were associated with longer overall survival (OS) (p < 0.05) and progression-free survival (PFS) (p < 0.05). Pretreatment IBIL was an independent prognostic factor for OS (hazard ratio [HR], 0.47; 95% confidence interval [CI] 0.28-0.79; p < 0.05) and PFS (HR, 0.53; 95% CI 0.33-0.85; p < 0.05)., Conclusion: Elevated pretreatment IBIL levels are correlated with improved OS and PFS, acting as an independent favorable prognostic indicator for AML., (© 2025 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

Objective: To determinate the association between of albumin, neutrophil-lymphocyte ratio and lymphocytes (NLR) with clinical stage in cervical cancers., Methods: Design a retrospective cross-sectional study of consecutive subjects diagnosed with cervical cancer for the first time. The Bethesda system was used for histological diagnosis and the subjects were stratified with the FIGO system, considering stages IA to IIB as localized; while, IIIA and IVB as advanced stages. Albumin, NLR and lymphocytes were evaluated as inflammatory biomarkers and the cut-off points generated by the ROC curves were albumin < 3 mg/dL, NLR ≥ 2.0 and lymphocytes < 1.2 10 3 /ul. The association was calculated by Odds Ratios (OR) with 95% confidence intervals., Results: A total of 152 patients were analyzed, with mean age of 49.3 ± 14.0 years. Epidermoid cancer was the most frequent in 70.6% and 51.3% were classified as advanced clinical stages. A bivariate analysis showed significant relationships between advanced clinical stages and albumin < 3 mg/dL with OR 5.72 (CI95% 2.62-12.4; p < 0.001); for NLR ≥ 2.0 an OR 2.53 (CI95% 1.34-4.89; p = 0.005) and for lymphocytes < 1.2 10 3 /ul of OR 3.39 (CI95% = 1.73-6.65; p < 0.001)., Conclusions: Albumin levels < 3 mg/dL, NLR ≥ 2.0 and lymphocytes < 1.2 10 3 /ul, were associated with advanced stages in subjects with cervical cancer., Competing Interests: Declarations. Conflict of interest: The authors declare that they have no competing interests. Ethical approval: This study was reviewed and approved by Research and Ethics Committee of the Hospital and all aspects of the study were performed according to the principles of the 1964 Declaration of Helsinki and its later amendments. Informed consent: Since this was a retrospective study that only used secondary data, informed consent was waived because we used anonymized retrospective data., (© 2024. The Author(s), under exclusive licence to Federación de Sociedades Españolas de Oncología (FESEO).)

Background: Individuals with normal weight obesity (NWO) often escape the attention of healthcare providers who may assume that a normal body mass index (BMI) correlates with low health risks. However, it remains unknown whether NWO increases the risk of breast cancer., Methods: This study included 22,257 and 52,506 pre- and postmenopausal females with normal BMI in the UK Biobank. NWO was defined as participants with a normal BMI (18.5-24.9 kg/m2) and an excess percent body fat (PBF > 33.3%). Cox proportional hazard models were used to investigate the associations of NWO and NWO-related biomarkers with incident breast cancer., Results: NWO was not associated with premenopausal breast cancer, whereas it was associated with a higher risk of postmenopausal breast cancer (hazard ratio = 1.19, 95% CI: 1.08-1.31). In our meta-analysis, per 5-unit increment in percent body fat level was linked to a 15% (95% CI: 10-19%) elevated risk of postmenopausal breast cancer in females with normal BMI. Stratified analyses showed a stronger positive association in females with higher genetic risk. In our NWO-biomarkers analyses, NWO was linked to 34 identified biomarkers, of which three inflammation markers (monocyte count, neutrophil count, and C-reactive protein), and one ketone body metabolite (β-Hydroxybutyrate) also indicated a positive association with postmenopausal breast cancer., Conclusions: NWO is associated with an increased risk of postmenopausal breast cancer, indicating that relying solely on BMI neglects the higher risk faced by non-obese postmenopausal women., Competing Interests: Competing interests: The author declares no competing interests. Ethics approval and consent to participate: The UK Biobank was approved by the North West Multi centre Research Ethics Committee (MREC) as a Research Tissue Bank (RTB) approval. All participants provided their informed written consent before participation. This study was performed in accordance with the Declaration of Helsinki., (© 2024. The Author(s).)

Background: Biomarkers for colorectal cancer (CRC) can complement population screening methods, but so far, few plasma proteins have been identified as biomarkers for CRC. This study aims to identify potential protein biomarkers and therapeutic targets for CRC within the proteome range., Methods: We extracted summary-level data of circulating protein from 7 published genome-wide association studies (GWASs) of plasma proteome for Mendelian randomization (MR), summary-data-based MR (SMR), and co-localization analyses to screen and validate proteins with causal effects in CRC. In addition, we further conducted druggability evaluation, prognosis analysis at the transcriptional level, and enrichment expression at the single-cell level, highlighting the important role of these plasma protein biomarkers in CRC., Results: We identified 117 plasma protein biomarkers associated with CRC risk, with 9 proteins showing stronger genetic correlations in Bayesian co-localization (PP.H4 > 0.70). Further, we found 26 protein-coding genes already used in targeted drug development and may potentially become therapeutic targets for CRC. In prognosis analysis, the encoding genes of plasma proteins exhibited consistent effects with MR analysis and can serve as prognostic biomarkers for CRC. Additionally, we also found that the differentially expressed proteins are mainly expressed in fibroblasts, endothelial cells, macrophages, and T cells., Conclusion: Our study has identified plasma protein biomarkers associated with CRC risk, which may complement population screening methods for CRC and achieve more precise treatment for patients., Competing Interests: Declarations. Conflict of interest: The authors declare that they have no conflict of interest. Ethical approval and consent to participate: Not applicable, as the data in this manuscript is sourced from previously published studies that have undergone ethical review by relevant institutions and informed consent from patients. Research involving human participants and animals and Informed consent: The data in this manuscript were derived from previously published studies in public databases that were ethically reviewed by the relevant authorities and for which informed consent was obtained from the patients. We have provided the necessary notes in the corresponding sections., (© 2024. The Author(s), under exclusive licence to Federación de Sociedades Españolas de Oncología (FESEO).)

Lymphoma is one of the leading causes of cancer and cancer deaths and yet has not been amenable to population screening. The role of methylated DNA markers (MDMs) in the detection of lymphoma has not been extensively studied. We aimed to discover, validate, and test tissue-derived MDMs of lymphoma in archival plasma specimens. Reduced representation bisulfite sequencing (RRBS) was performed on a discovery set of frozen tissues. MDMs identified were converted to methylation-specific PCR assays and validated on independent formalin-fixed, paraffin-embedded (FFPE) tissues. Target enrichment long-probe quantitative-amplified signal (TELQAS) assays were developed and assayed in plasma-extracted, bisulfite-converted DNA from independent treatment-naïve lymphoma patients and healthy controls. Prediction of cancer status was modeled using random forest model with in silico cross-validation. After discovery and validation in tissue, 16 TELQAS assays (ZNF503, VWA5B1, HOXA9, GABRG3, ITGA5, MAX.chr17.7190, BNC1, CDK20, MAX.chr4.4069, TPBG, DNAH14, SYT6, CACNG8, FAM110B, ADRA1D, and NRN1) were selected for testing in plasma. These detected 78% (95% CI, 74%-82%) of lymphoma cases at 90% specificity. Excluding marginal zone and T-cell lymphomas, sensitivity increased to 84% (80%-88%). MDMs in plasma show promise to detect lymphoma and are candidates for inclusion in multi-cancer detection studies., (© 2024 The Author(s). American Journal of Hematology published by Wiley Periodicals LLC.)

Background: Neoadjuvant chemotherapy (NAC) can provide improved survival outcomes in pancreatic ductal adenocarcinoma (PDAC) patients who respond to treatment, but currently available biomarkers cannot reliably predict NAC response. This study aimed to determine the potential of a previously identified diagnostic and prognostic biomarker panel (i.e. Ca-125, S100A2, S100A4, Mesothelin and Ca19-9) for the monitoring of NAC-response in PDAC patients., Methods: This single-centre, retrospective study, utilised serum from NAC treated PDAC patients to determine the levels of biomarkers by Enzyme-Linked Immunosorbent Assay (ELISA). The percentage of the tumour bed occupied by viable carcinoma (PVC) was used to divide patients into good (PVC < 50%) and poor (PVC ≥ 50%) NAC-responders. Statistical analysis was performed to measure the ability of individual biomarkers and a biomarker panel in NAC treatment response and patient survival., Results: Serum specimens from a total of 108 PDAC patients were assessed. Ca-125, Ca19-9 and S100A2 showed a significant positive correlation with PVC. Ca-125 demonstrated a superior ability to monitor NAC treatment response (Area under receiver operating curve (AUC): .6954) compared to the more widely used clinical biomarker, Ca19-9 (AUC: .6291). A panel of Ca-125 and Ca19-9 showed good ability to monitor NAC response in PDAC patients (AUC: .7349). Patients with high levels of both Ca-125 and Ca19-9 were shown to have the poorest overall survival (median overall survival: 17 vs. 30 months)., Conclusion: A serum biomarker panel of Ca-125 and Ca19-9 could be used for effective clinical management of PDAC patients undergoing NAC treatment., (© 2024 Stichting European Society for Clinical Investigation Journal Foundation. Published by John Wiley & Sons Ltd.)

Objectives: Liquid biopsy, with its noninvasive nature and ability to detect tumor-specific genetic alterations, emerges as an ideal biomarker for monitoring recurrences for locally advanced rectal cancer (LARC). Completed studies have small sample sizes and different experimental methods. To consolidate and assess the collective evidence regarding the prognostic role of circulating DNA (ctDNA) detection in LARC patients undergoing neoadjuvant chemoradiotherapy (nCRT)., Methods: Computerized bibliographic searches of MEDLINE and CANCERLIT (2000 to 2023) were supplemented with hand searches of reference lists. Study selection: studies evaluating oncological outcomes of patients with LARC treated with a nCRT comparing patients with positive and negative liquid biopsy at baseline and after nCRT. Data extraction: data on population, intervention, and outcomes were extracted from each study, in accordance with the intention to treat method, by 2 independent observers, and combined using the DerSimonian method and Laird method., Results: Nine studies follow inclusion criteria including 678 patients treated with nCRT. The pooled RD rate of ctDNA negative between measure at baseline and after nCRT is statistically significant 61% (95% CI: 53-70, P =0.0002). The hazard ratio (HR) of progression-free survival between ct-DNA negative and positive is significant 7.41 (95% CI: 4.87-11.289, P <0.00001)., Conclusions: ctDNA can identify patients with different recurrence risks following nCRT and assess prognosis in patients with LARC. Further prospective study is necessary to determine the utility of ctDNA in personalised therapy for patients with LARC., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background & Aims: Better surveillance tests for hepatocellular carcinoma (HCC) are needed. The GALAD score (gender, age, α-fetoprotein [AFP] L3, AFP, and des-γ carboxyprothrombin) has been shown to have excellent sensitivity and specificity for HCC in phase 2 studies. We performed a phase 3 biomarker validation study to compare GALAD with AFP in detecting HCC., Methods: This is a prospective study of patients with cirrhosis enrolled at 7 centers. Surveillance for HCC was performed every 6 months at each site, and HCC diagnosis was confirmed per American Association for the Study of Liver Diseases guidelines. Blood for biomarker research was obtained at each follow-up visit and stored in a biorepository. Measurements of AFP, AFP-L3, and des-γ carboxyprothrombin) were performed in a FujiFilm laboratory by staff blinded to clinical data. The performance of GALAD in detecting HCC was retrospectively evaluated within 12 months before the clinical diagnosis. All analyses were conducted by an unblinded statistician in the Early Detection Research Network data management and coordinating center., Results: A total of 1,558 patients with cirrhosis were enrolled and followed for a median of 2.2 years. A total of 109 patients developed HCC (76 very early or early stage), with an annual incident rate of 2.4%. The areas under the curve for AFP and GALAD within 12 months before HCC were 0.66 and 0.78 (P < .001), respectively. Using a cutoff for GALAD of -1.36, the specificity was 82%, and the sensitivity at 12 months before HCC diagnosis was 62%. For comparison, performance of AFP at 82% specificity showed 41% sensitivity at 12 months before HCC diagnosis (P = .001)., Conclusions: GALAD score, compared to AFP, improves the detection of HCC within 12 months before the actual diagnosis., (Copyright © 2025 AGA Institute. All rights reserved.)

Small cell lung cancer (SCLC) constitutes around 15% of lung cancer cases and stands as the primary cause of cancer-related fatalities in men and the second leading cause in women globally. In this study, our objective was to evaluate the levels of C-reactive protein (CRP) and procalcitonin (PCT) in newly diagnosed extensive-stage SCLC patients without evidence of infection. We aimed to demonstrate that elevated CRP and PCT levels may not solely indicate infection but could also be elevated in malignancies. Furthermore, we sought to correlate these marker levels with patient and disease characteristics to elucidate the relationship between these inflammation markers and disease progression. A total of 115 patients who were pathologically and radiologically diagnosed with extensive-stage SCLC between January 2020 and December 2022 and who had received no prior treatment were included in the study. The Kaplan-Meier analysis revealed a median progression-free survival (PFS) of 7.46 months [95% confidence interval (CI), 6.85-8.07] and a median overall survival (OS) of 10.50 months (95% CI, 8.69-12.30) for all patients. In the group with elevated PCT, the median PFS was 6.73 months (95% CI, 3.92-9.54), whereas it was 7.86 months (95% CI, 7.13-8.59) in the group with normal PCT ( P  = 0.002). Similarly, the median OS was 9.10 months (95% CI, 5.61-12.58) in the elevated PCT group and 11.66 months (95% CI, 9.59-13.74) in the normal PCT group ( P  = 0.006). Patients with elevated procalcitonin (PRC) levels at the time of diagnosis exhibited shorter PFS and OS durations compared to patients with normal PRC levels. Furthermore, elevated CRP has also been demonstrated to correlate with poorer prognosis in extensive-stage SCLC., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Herein, a dual-mode fluorometric and colorimetric biosensor for Pax-5a gene was developed based on zinc-doped molybdenum disulfide quantum dots (Zn-MoS 2 QDs) by coupling exonuclease-assisted recycling amplification and peroxidase-mimic DNAzyme. In the presence of Pax-5a gene, the exonuclease III can cleave the duplexes formed by Pax-5a gene and the hairpin DNA (HP), releasing the output DNA (oDNA). G-rich DNA and magnetic beads (MBs) labeled with capture DNA (cDNA) can hybridize with oDNA to form the MBs-cDNA/oDNA/G-rich DNA sandwich complex. The remaining G-rich DNA in the supernatant through magnetic separation could bind hemin to produce G-quadruplex/hemin peroxidase-mimicking DNAzyme, which catalyzed the oxidization of 3,3'-diaminobenzidine (DAB) by H 2 O 2 . The generated brown oxidation product (oxDAB) had a distinct absorption peak at 464 nm and could quench the fluorescence of Zn-MoS 2 QDs at 406 nm. The high peroxidase activity of DNAzyme, recycling amplification strategy and magnetic separation technique led to excellent sensitivity and specificity of this detection platform. The detection limits of Pax-5a gene by fluorometric and colorimetric methods were 0.52 pM and 1.12 pM, respectively. Furthermore, this sensing system was successfully applied to Pax-5a gene determination in human serum samples, which had promising potential in biochemical analysis and clinical diagnosis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Whether radiation should be added to neoadjuvant treatment remains controversial, and liquid biopsy has not been reported to predict radioresistance in pancreatic cancer (PC). We aimed to identify microRNAs (miRNAs) governing radioresistance in PC by utilizing peripheral plasma exosome samples and to verify their usefulness as biomarkers., Methods: miRNA microarray analysis was conducted using pretreatment peripheral plasma exosomes from 10 patients with PC receiving neoadjuvant chemoradiotherapy (NACRT) in the discovery cohort. Patients were categorized into two groups (good and poor responders) based on treatment responses, and candidate miRNAs exhibiting differential expression between the two groups were identified. The radiosensitivity of PC cells was examined after miR-6855-5p overexpression. Next-generation sequencing (NGS) and TargetScan were used to explore the mechanisms of radioresistance. We investigated the correlation between miR-6855-5p expression levels in the pretreatment peripheral plasma exosomes of 28 patients in the validation cohort and the response to NACRT., Results: miR-6855-5p expression was higher in poor responders than in good responders. miR-6855-5p induces radioresistance in PC cells. NGS showed that epithelial-mesenchymal transition (EMT) was involved in miR-6855-5p-related radioresistance. Forkhead box protein A1 (FOXA1) was identified as a direct target of miR-6855-5p using NGS and TargetScan. Clinical examination of samples from the validation cohort revealed a tendency for patients with higher expression of miR-6855-5p in peripheral plasma exosomes to exhibit increased radioresistance (r = -0.5964)., Conclusions: miR-6855-5p regulates the radioresistance of PC by inducing EMT via suppressing FOXA1, and miR-6855-5p in peripheral plasma exosomes may be a biomarker for radioresistance of PC., Competing Interests: Ethics Approval and Consent to Participate: This study was approved by the Institutional Review Board (IRB) of Osaka University Hospital (IRB No. 08226-12) and adhered to the principles outlined in the Declaration of Helsinki. Patient Consent for Publication: Written informed consent was obtained from all blood donors. Disclosures: Shogo Kobayashi received honoraria and speaker fees from AstraZeneca, Ethicon Inc., Intuitive, Olympus, and Taiho Pharmaceutical. Hiroki Ueda, Hidenori Takahashi, Masahiko Kubo, Kazuki Sasaki, Yoshifumi Iwagami, Daisaku Yamada, Yoshito Tomimaru, Tadafumi Asaoka, Takehiro Noda, Junzo Shimizu, Yuichiro Doki, and Hidetoshi Eguchi have no conflicts of interest that may be relevant to the contents of this study., (© 2024. Society of Surgical Oncology.)

Background: Perioperative blood transfusion (BT) is frequent in the treatment of gastric cancer (GC), but its effects on the prognosis of GC remains controversial. In this study, we aimed to further confirm the relationship of perioperative BT with GC overall survival and to evaluate the predictive value of microRNA-338-3p (miR-338-3p) for the prognosis of GC patients who received perioperative BT., Methods: Clinical data and serum samples were collected and analyzed from 246 patients with GC. Five-year follow-up survival information was assessed by Kaplan-Meier survival analysis. miR-338-3p relative expression was assessed by RT-qPCR, and its relationship with the prognosis of GC patients, who received perioperative BT, was evaluated using Kaplan-Meier curves and Cox regression analysis., Results: GC patients received perioperative BT had poor 5 year survival than those without BT. In patients received BT, miR-338-3p expression was higher in survival cases than died population and high miR-338-3p was independently associated with better overall survival prognosis., Conclusion: Perioperative BT is related with poor prognosis in GC patients and miR-338-3p may be a prognostic biomarker for GC patients received perioperative BT. BT in perioperative GC patients should be cautious, especially for those with low levels of miR-338-3p., Competing Interests: Declarations. Conflict of interest: The authors declare that they have no competing interests. Ethical approval and consent to participate: The experimental procedures were all in accordance with the guideline of the Ethics Committee of Zibo First Hospital and has approved by the Ethics Committee of Zibo First Hospital. This study complies with the Declaration of Helsinki. A signed written informed consent was obtained from each patient. Consent for publication: Not applicable., (© 2024. The Author(s), under exclusive licence to Federación de Sociedades Españolas de Oncología (FESEO).)

Objectives: To measure dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) biomarker repeatability in patients with non-small cell lung cancer (NSCLC). To use these statistics to identify which individual target lesions show early biological response., Materials and Methods: A single-centre, prospective DCE-MRI study was performed between September 2015 and April 2017. Patients with NSCLC were scanned before standard-of-care radiotherapy to evaluate biomarker repeatability and two weeks into therapy to evaluate biological response. Volume transfer constant (K trans ), extravascular extracellular space volume fraction (v e ) and plasma volume fraction (v p ) were measured at each timepoint along with tumour volume. Repeatability was assessed using a within-subject coefficient of variation (wCV) and repeatability coefficient (RC). Cohort treatment effects on biomarkers were estimated using mixed-effects models. RC limits of agreement revealed which individual target lesions changed beyond that expected with biomarker daily variation., Results: Fourteen patients (mean age, 67 years +/- 12, 8 men) had 22 evaluable lesions (12 primary tumours, 8 nodal metastases, 2 distant metastases). The wCV (in 8/14 patients) was between 9.16% to 17.02% for all biomarkers except for v p , which was 42.44%. Cohort-level changes were significant for K trans and v e (p < 0.001) and tumour volume (p = 0.002). K trans and tumour volume consistently showed the greatest number of individual lesions showing biological response. In distinction, no individual lesions had a real change in v e despite the cohort-level change., Conclusion: Identifying individual early biological responders provided additional information to that derived from conventional cohort cohort-level statistics, helping to prioritise which parameters would be best taken forward into future studies., Clinical Relevance Statement: Dynamic contrast-enhanced magnetic resonance imaging biomarkers K trans and tumour volume are repeatable and detect early treatment-induced changes at both cohort and individual lesion levels, supporting their use in further evaluation of radiotherapy and targeted therapeutics., Key Points: Few literature studies report quantitative imaging biomarker precision, by measuring repeatability or reproducibility. Several DCE-MRI biomarkers of lung cancer tumour microenvironment were highly repeatable. Repeatability coefficient measurements enabled lesion-specific evaluation of early biological response to therapy, improving conventional assessment., Competing Interests: Compliance with ethical standards. Guarantor: The scientific guarantor of this publication is James O’Connor. Conflict of interest: The authors of this manuscript declare relationships with the following companies: Geoff Parker has ownership and shares interests with Bioxydyn Ltd. The remaining authors declare no conflicts of interest. Statistics and biometry: One of the authors has significant statistical expertise (Nuria Porta). Informed consent: Written informed consent was obtained from all subjects (patients) in this study. Ethical approval: Institutional Review Board approval was obtained. Study subjects or cohorts overlap: Subjects were included in a separate study ( https://pubmed.ncbi.nlm.nih.gov/31053599/ ) but the data reported here are entirely independent and do not overlap. Methodology: Prospective Experimental Performed at one institution, (© 2024. The Author(s).)

Purpose: To evaluate the surveillance value of circulating tumor DNA (ctDNA) for detecting distant metastasis and indicating systemic therapeutic efficacy in conjunctival melanoma (CoM)., Design: Retrospective, observational case series., Methods: From July 2021 to June 2023, 30 CoM patients in our center underwent plasma ctDNA assessment, out of which 12 individuals presented with distant metastases. We employed a 437-gene panel containing common mutations in CoM and common drug-sensitive mutations using next-generation sequencing (NGS) technology to analyze ctDNA mutations in plasma. Clinical and radiological records were used to assess tumor status. The relationship between ctDNA characteristics, tissue gene mutations, and clinical manifestations were explored., Results: CoM-related driver mutations were detected in ctDNA of 11 patients with distant metastasis. The ctDNA were highly consistent with tissue sequencing, mutual driver mutation including BRAF, NRAS, KRAS, NF1, CTNNB1, and TP53 mutation. those with a higher VAF had shorter progression-free survival (PFS, p = .0475) and overall survival (OS, p = .0043). The ctDNA variant allele fraction (VAF) was not correlated with the sum of the longest diameters (SLD, p = .8192) in distant metastasis patients., Conclusions: Positive plasma ctDNA reflected the presence of metastases. The ctDNA could be used as a complement or alternative to tissue sequencing. High VAF ctDNA might indicate rapid disease progression in distant metastasis patients., (Copyright © 2024. Published by Elsevier Inc.)

Brain metastases account for a significant number of cancer-related deaths with poor prognosis and limited treatment options. Current diagnostic methods have limitations in resolution, sensitivity, inability to differentiate between primary and metastatic brain tumors, and invasiveness. Liquid biopsy is a promising non-invasive alternative; however, current approaches have shown limited efficacy for diagnosing brain metastases due to biomarker instability and low levels of detectable tumor-specific biomarkers. This study introduces an innovative liquid biopsy technique using extracellular vesicles (EVs) as a biomarker for brain metastases, employing the Brain nanoMET sensor. The sensor was fabricated through an ultrashort femtosecond laser ablation process and provides excellent surface-enhanced Raman Scattering functionality. We developed an in vitro model of metastatic tumors to understand the tumor microenvironment and secretomes influencing brain metastases from breast and lung cancers. Molecular profiling of EVs derived from brain-seeking metastatic tumors revealed unique, brain-specific signatures, which were also validated in the peripheral circulation of brain metastasis patients. Compared to primary brain tumor EVs, we also observed an upregulation of PD-L1 marker in the metastatic EVs. A machine learning model trained on these EV molecular profiles achieved 97% sensitivity in differentiating metastatic brain cancer from primary brain cancer, with 94% accuracy in predicting the primary tissue of origin for breast metastasis and 100% accuracy for lung metastasis. The results from this pilot validation suggest that this technique holds significant potential for improving metastasis diagnosis and targeted treatment strategies for brain metastases, addressing a critical unmet need in neuro-oncology., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Krishnan Venkatakrishnan reports financial support was provided by Natural Sciences and Engineering Research Council of Canada. Bo Tan reports financial support was provided by Natural Sciences and Engineering Research Council of Canada., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background and Aims: The original hepatocellular carcinoma early detection screening (HES) score, which combines alpha-fetoprotein (AFP) with age, alanine aminotransferase, and platelets, has better performance than AFP alone for early HCC detection. We have developed HES V2.0 by adding AFP-L3 and des-gamma-carboxy prothrombin to the score and compared its performance to GALAD and ASAP scores among patients with cirrhosis., Approach and Results: We conducted a prospective-specimen collection, retrospective-blinded-evaluation phase 3 biomarker cohort study in patients with cirrhosis enrolled in imaging and AFP surveillance. True-positive rate (TPR)/sensitivity and false-positive rate for any or early HCC were calculated for GALAD, ASAP, and HES V2.0 scores within 6, 12, and 24 months of HCC diagnosis. We calculated the AUROC curve and estimated TPR based on an optimal threshold at a fixed false-positive rate of 10%. We analyzed 2331 patients, of whom 125 developed HCC (71% in the early stages). For any HCC, HES V2.0 had higher TPR than GALAD overall (+7.2%), at 6 months (+3.6%), at 12 months (+7.2%), and 24 months (+13.0%) before HCC diagnosis. HES V2.0 had higher TPR than ASAP for all time points (+5.9% to +12.0%). For early HCC, HES V2.0 had higher sensitivity/TPR than GALAD overall (+6.7%), at 12 months (+6.3%), and 24 months (+14.6%) but not at 6 months (+0.0%) and higher than ASAP for all time points (+13.4% to +18.0%)., Conclusions: In a prospective cohort study, HES V2.0 had a significantly higher performance for identifying new HCC, including early stage, than GALAD or ASAP., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Alterations within the tryptophan-kynurenine metabolic pathway have been linked to the etiology of colorectal cancer (CRC), but the relevance of this pathway for prognostic outcomes in CRC patients needs further elucidation. Therefore, we investigated associations between circulating concentrations of tryptophan-kynurenine pathway metabolites and all-cause mortality among CRC patients. This study utilizes data from 2102 stage I-III CRC patients participating in six prospective cohorts involved in the international FOCUS Consortium. Preoperative circulating concentrations of tryptophan, kynurenine, kynurenic acid (KA), 3-hydroxykynurenine (HK), xanthurenic acid (XA), 3-hydroxyanthranilic acid (HAA), anthranilic acid (AA), picolinic acid (PA), and quinolinic acid (QA) were measured by liquid chromatography-tandem mass spectrometry. Using Cox proportional hazards regression, we examined associations of above-mentioned metabolites with all-cause mortality, adjusted for potential confounders. During a median follow-up of 3.2 years (interquartile range: 2.2-4.9), 290 patients (13.8%) deceased. Higher blood concentrations of tryptophan, XA, and PA were associated with a lower risk of all-cause mortality (per doubling in concentrations: tryptophan: HR = 0.56; 95%CI:0.41,0.76, XA: HR = 0.74; 95%CI:0.64,0.85, PA: HR = 0.76; 95%CI:0.64,0.92), while higher concentrations of HK and QA were associated with an increased risk of death (per doubling in concentrations: HK: HR = 1.80; 95%CI:1.47,2.21, QA: HR = 1.31; 95%CI:1.05,1.63). A higher kynurenine-to-tryptophan ratio, a marker of cell-mediated immune activation, was associated with an increased risk of death (per doubling: HR = 2.07; 95%CI:1.52,2.83). In conclusion, tryptophan-kynurenine pathway metabolites may be prognostic markers of survival in CRC patients., (© 2024 The Author(s). International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

Gastric cancer (GC) poses a significant global health challenge, demanding a detailed exploration of its molecular landscape. Studies suggest that exposure to environmental pollutants can lead to changes in microRNA (miRNA) expression patterns, which may contribute to the development and progression of GC. MiRNAs have emerged as crucial regulators implicated in GC pathogenesis. The largest GC serum miRNA dataset to date, comprising 1417 non-cancer controls and 1417 GC samples was used. We conducted a comprehensive analysis of miRNA expression profiles. Differential expression analysis, co-expression network construction, and machine learning models were employed to identify key serum miRNAs and their association with clinical parameters. Weighted Gene Co-expression Network Analysis (WGCNA) and immune infiltration analysis were used to validate the importance of the key miRNA. A total of 1766 differentially expressed miRNAs were identified, with miR-1290, miR-1246, and miR-451a among the top up-regulated, and miR-6875-5p, miR-6784-5p, miR-1228-5p, and miR-6765-5p among the top down-regulated. WGCNA revealed that modules M1 and M5 were significantly associated with GC subtypes and disease status. MiRNA-target gene network analysis identified prognostically significant genes TP53, EMCN, CBX8, and ALDH1A3. Machine learning models LASSO, SVM, randomforest, and XGBOOST demonstrated the diagnostic potential of miRNA profiles. Tissue and serum miR-187 emerged as an independent prognostic factor, influencing patient survival across clinical parameters. Gene expression and immune cell infiltration were different in tissues stratified by miR-187 expression. In summary, the integration of differential gene expression, co-expression analysis, and immune cell profiling provided insights into the molecular intricacies of GC progression., (© 2024 Wiley Periodicals LLC.)

In the setting of hepatocellular carcinoma (HCC) surveillance, a range of observations can be identified. Often, imaging findings and biochemical results are consistent with the diagnosis of HCC. However, challenges in HCC surveillance can arise in different clinical contexts, particularly when imaging results and tumor biomarkers are discordant. In this article, the authors describe 5 clinical scenarios based on our experiences in which additional evaluation was necessary to determine whether HCC was present or not., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: The prevalence of lung cancer among individuals afflicted with interstitial pneumonia (IP) stands at approximately 20%. The early detection of lung cancer via chest computed tomography (CT) surveillance proves challenging in IP patients. Our investigation sought to identify a potential biomarker capable of providing early indications of the presence of lung tumors in such patients., Materials and Methods: We examined the attributes of serum tumor markers, imaging characteristics, and histological findings in individuals diagnosed with IP, both with and without concurrent lung cancer., Results: 106 patients diagnosed with IP were included in the study, comprising 36 individuals with concurrent lung cancer and 70 patients solely diagnosed with IP. Serum concentrations of CEA and CA12-5 were notably elevated in IP patients with lung cancer, compared to those with IP alone. Logistic regression analyses revealed that, in comparison to IP patients within the first quartile of CEA levels, the relative risk of developing lung cancer associated with IP escalated by 4.0-fold, 3.1-fold, 11.0-fold, and 13.3-fold in the second, third, fourth, and fifth quartiles, respectively. Upon controlling for gender and age, statistical significance in risk was observed solely for the fourth and fifth quartiles. Receiver operating characteristic (ROC) curve analysis conducted in patients diagnosed with ILD-CA identified a CEA cutoff point of 6.9 ng/mL, demonstrating sensitivities of 61.1% and specificities of 78.5%. The area under the curve was calculated as 0.7(95% CI: 0.63-0.81)., Conclusion: The serum levels of CEA were notably elevated in IP patients with concurrent lung cancer in contrast to those who were just suffering from IP. The heightened serum CEA levels correlate with an escalated risk of cancer occurrence among IP patients, suggesting that serum CEA levels could potentially serve as an indicative marker for the presence of cancer in IP patients., Competing Interests: Declarations. Conflict of interest: The authors declare no potential conflicts of interest. Ethical approval and consent to participate: This study was approved by the Ethics committee of People’ Hospital Affiliated to Fujian University of Traditional Chinese Medicine. Consent for publication: Not applicable., (© 2024. The Author(s), under exclusive licence to Federación de Sociedades Españolas de Oncología (FESEO).)

Background: Carcinoembryonic antigen (CEA) levels may vary with administration and discontinuation of pre-hepatectomy chemotherapy in patients undergoing resection of colorectal cancer liver metastases (CLM). The prognostic significance of these changes, termed CEA dynamics, is unclear., Patients and Methods: Consecutive patients undergoing hepatectomy for CLM (2001-2021) at a comprehensive cancer center were included. CEA dynamics were classified as CEA normal (CEA < 5 ng/mL before, during, and after chemotherapy), CEA decrease (elevated CEA levels that drop during and after chemotherapy), and CEA rebound (elevated CEA levels that drop during chemotherapy but rebound upon discontinuation). Recurrence-free (RFS), hepatic-specific disease-free (hDFS), and overall survival (OS) were compared across CEA dynamics groups., Results: Of 903 patients, 254 (28%) were CEA normal, 423 (47%) were CEA decrease, and 226 (25%) were CEA rebound. Median RFS was 15.9 months, median hDFS was not reached, and median OS was 11.9 years for CEA normal patients. By comparison, CEA decrease and CEA rebound patients had shorter median RFS (12.2 months, P = 0.002 and 7.4 months, P < 0.001, respectively), shorter median hDFS (29.1 months, P = 0.003 and 14.8 months, P < 0.001, respectively), and shorter median OS (7.1 years, P = 0.131, and 4.9 years, P < 0.001, respectively). On multivariable analysis, CEA rebound was an independent predictor of worse RFS [hazard ratio (HR) 1.50, 95% confidence interval (CI) 1.16-1.93], hDFS (HR 1.39, 95% CI 1.03-1.88), and OS (HR 1.79, 95% CI 1.18-2.73). Among patients with CEA rebound, RAS-BRAF/TP53 comutation and multiple tumors predicted worse OS while APC mutation predicted improved OS., Conclusion: CEA rebound between pre-hepatectomy chemotherapy discontinuation and CLM resection is associated with worse oncologic outcomes, particularly in patients with aggressive tumor biology, and may help frame patient and surgeon expectations ahead of CLM resection., Competing Interests: Discolsure: The authors have no conflict of interest to disclose. The authors are willing to make their data, analytical methods, and study materials available to other researchers upon reasonable request, including relevant ethical and legal statements, to the corresponding author., (© 2024. Society of Surgical Oncology.)

Purpose: Non-small cell lung cancer (NSCLC) is a widespread and serious global malignancy. This study aimed to examine the clinical relevance of serum exosomal SNORD116 and SNORA21 as novel diagnostic biomarkers for NSCLC., Methods: Serum exosomes from 226 healthy controls and 305 NSCLC patients were isolated by ultracentrifugation. Characterization of exosomes was conducted by qNano, transmission electron microscopy (TEM) and Western immunoblotting. RT-PCR revealed snoRNAs that were differentially expressed. Receiver operating characteristic (ROC) analysis was used to assess the diagnostic performance., Results: In NSCLC patients, the levels of serum exosomal SNORD116 and SNORA21 were significantly reduced compared to those in healthy controls (P < 0.0001 for both). ROC curves showed AUC values of 0.738 and 0.761. By combining SNORD116 and SNORA21 with traditional blood biomarkers CYFRA21-1 and carcinoembryonic antigen (CEA), the AUC increased to 0.917. Moreover, these two exosomal snoRNAs distinguished between patients with metastatic NSCLC (n = 132) and those with non-metastatic NSCLC (n = 173) significantly (P < 0.0001 for both). The ROC curves gave AUC values of 0.743 and 0.694, respectively. The combined analysis raised the AUC to 0.751. The diagnostic power of these two exosomal snoRNAs combined with CYFRA21-1 and CEA increased to 0.784., Conclusion: This study demonstrated that serum exosomal SNORD116 and SNORA21 can be used as potential promising non-invasive diagnostic biomarkers for NSCLC., Competing Interests: Declarations. Conflict of interest: No conflict of interest/competing interests to declare. Ethical approval, research involving human participants and animals and informed consent: The studies involving human participants were reviewed and approved by the Affiliated Taian City Central Hospital of Qingdao University (Approval number: 2021-04-02). All patients/participants gave written informed consent in accordance with the Declaration of Helsinki. Consent to participate: All authors have their consent to participate., (© 2024. The Author(s), under exclusive licence to Federación de Sociedades Españolas de Oncología (FESEO).)

Early diagnosis and screening of tumor markers are essential for effective cancer treatment and improve the treatment efficiency and prognosis of tumor recurrence and metastasis. In this study, a split-ring resonator (SRR) circuit based on an interdigital electrode structure was developed and applied to microwave biosensors along with machine learning to detect extremely low concentrations of Carcinoembryonic Antigen (CEA). CEA was detected using a microwave sensor operating at a resonance frequency of 4.33 GHz. When the microwave sensor is exposed to CEA analytes, it generates a new frequency in the range of 1-2 GHz. The position and intensity of the newly generated frequency can be used to characterize and predict the concentration of the CEA solution. The proposed sensor exhibits excellent resonance linearity for various concentrations of CEA (R 2  = 0.999), as well as a very low detection limit (39 pg/mL) and high sensitivity (27.5 MHz/(ng/mL)). A machine learning approach was implemented to predict the CEA concentration in blood samples. The results showed close concurrence with the CEA concentration detected by the sensor. Western Blot (WB) was used to compare the CEA contents of four different cell types, and a biosensor was used for validation; the results of the two experiments showed good agreement. This is the first demonstration of the validation of biosensor reliability at the cellular level. The proposed concept exhibits outstanding detection performance with convenient and rapid tumor marker detection. Hence, it has important implications as an auxiliary diagnosis method for cancer., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Introduction: Our aim was to assess parameters derived from preoperative blood tests as diagnostic or prognostic markers in patients with operable hepatocellular carcinoma (HCC)., Methods: We included 210 patients who underwent liver resection as the first treatment for suspected hepatocellular adenoma (HCA) or HCC (January 2010-December 2022). Parameters originated from preoperative complete blood count and biochemical blood tests were examined for associations with clinicopathological parameters and survival., Results: There were 31 cases of HCA and 179 cases of HCC. Fibrosis-4 index (FIB-4)≥0.77 provided the best diagnostic accuracy for differentiating between HCA and HCC [area under the curve: 0.914, P  < 0.001, sensitivity: 93.8%, specificity: 82.8%, positive predictive value (PPV): 96.9%, negative predictive value (NPV): 69.9%]. Patients with T2-T4 tumours had higher levels of aspartate aminotransferase to alanine aminotransferase ratio (AST/ALT) ( P  < 0.001), liver function tests index ( P  = 0.005), platelets-liver function tests index (PLFTI) ( P  = 0.011), and α-fetoprotein (AFP) ( P  < 0.001), but the diagnostic accuracy was mediocre. Patients with moderately or poorly differentiated tumours had higher levels of FIB-4 ( P  = 0.023), and AFP ( P  = 0.001), providing high PPV (89.4 and 95.1%, respectively). Albumin to alkaline phosphatase ratio (ALB/ALP)>0.508 [hazard ratio (HR): 0.501, P  = 0.009], FIB-4>1.41 (HR: 2.272, P  = 0.007), PLFTI>0.087 (HR: 1.849, P  = 0.016), and AFP>3.1 (HR: 3.066, P  = 0.006) provided statistically significant results in relation to disease-free survival, and ALB/ALP>0.389 (HR: 0.505, P  = 0.036) provided statistically significant results in relation to overall survival., Conclusion: Preoperative blood tests provide useful information in treatment-naive surgical candidates with suspected HCC regarding distinguishing from HCA, tumour differentiation, and risk of disease recurrence and death., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Neuroblastoma (NBL), is the most common, non-CNS solid tumor of childhood. This disease presents with unique biological and clinical challenges necessitating accurate diagnosis, prognosis assessment, treatment, and vigilant monitoring. Liquid biopsy is an upcoming, innovative, and non-invasive diagnostic modality. It has the potential to detect tumors and perform therapeutic monitoring through the analysis of circulating biomarkers in blood, urine, saliva, and other bodily fluids., Methodology: This scoping review offers an in-depth exploration, of the current landscape of liquid biopsy-based biomarkers in NBL. The review looks at the clinical implications, prevalent challenges, and future outlook of their clinical applications in NBL. The scoping review adhered to the guidelines of the PRISMA extension for scoping reviews, known as PRISMA-ScR, as the skeletal framework. The review involved comprehensive searches for liquid biopsy-based biomarkers in NBL across multiple databases, including PUBMED, EMBASE, SCOPUS, and WEB of Science, without restrictions., Results: The scoping review process uncovered a significant body of literature (n = 201) that underwent meticulous scrutiny, ultimately leading to the final selection of studies (n = 15). The liquid biopsy biomarkers included circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), exosomes, and other entities in bodily fluids. Their evaluation focused on associations with clinical outcomes such as overall survival, event-free survival, and risk stratification in NBL., Conclusion: Our findings highlight the potential of liquid biopsy biomarkers to revolutionize NBL diagnosis and therapeutic monitoring. This rapidly evolving frontier in pediatric oncology suggests significant advancements in precision medicine for the management of NBL., Competing Interests: Conflict of interest All authors have no conflicts of interest to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Ovarian cancer, known as "silent killer", is a gynocological cancer with high mortality that usually diagnosed in the late stages. Gold standard immunoassay technique is evaluation of CA-125 levels which is not merely specific to ovarian cancer. Therefore, there is a need for sensitive determination of more specific biomarkers. miR-200 family is RNA nucleic acids that known to be upregulated in the presence of ovarian cancer. Since diagnosis based on a single biomarker is prone to generate misleading results, it is important to develop point-of-care systems that allow diagnosis of multiple miRNAs. Herein, an electrochemical nanobiosensor platform was developed for the multiplexed and simultaneous detection of miR-200c and miR-141. Biorecognition part was constitutued of methylene blue and ferrocene labeled hairpin DNA probes immobilized onto carboxylated graphene oxide modified pencil graphite electrodes. Their hybridization with miRNAs were examined upon "signal-off" approach using Square Wave Voltammetry. The platform demonstrated a linear detection range of 0.1 pM to 10 nM for both miR-141 and miR-200c, with low detection limits of 0.029 pM and 0.026 pM, respectively. We assume that the developed biosensor platform may pave the way in early diagnosis of the disease and the development of more effective treatment strategies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: Pancreatic cancer (PC) is a highly aggressive malignancy with poor prognosis and high mortality rate. Identifying reliable biomarkers for the early diagnosis and treatment is urgently needed. This study aims to comprehensively evaluate the diagnostic and prognostic value of DUPAN-2 in PC through a meta-analysis., Methods: We systematically searched PubMed, Embase, and other databases for studies related to DUPAN-2 and its prognostic and diagnostic relevance in PC, covering publications up to August 2024. We used pooled hazard ratios (HRs) to evaluate the prognostic value of DUPAN-2 in PC, the summary receiver operating characteristic (SROC) curve and the area under the curve (AUC) to assess diagnostic performance, while pooled odds ratios (ORs) analyzed associations with clinicopathological features., Results: A total of 22 studies involving 4765 patients were included in this meta-analysis, with 11 studies focusing on diagnostic analysis, 10 on prognostic analysis, and 3 on clinicopathological features. The diagnostic meta-analysis revealed a pooled sensitivity of 0.63 (95 % CI: 0.56-0.69), a pooled specificity of 0.98 (95 % CI: 0.95-0.99), and an AUC of 0.83 (95 % CI: 0.79-0.86). Subgroup analysis indicated that a DUPAN-2 threshold at 150 U/mL achieved the highest diagnostic performance. The prognostic meta-analysis demonstrated that elevated DUPAN-2 levels were associated with poorer OS (HR = 1.70, 95 % CI: 1.36-2.14) and PFS (HR = 1.33, 95 % CI: 1.14-1.56). Additionally, the clinicopathological features meta-analysis showed that elevated DUPAN-2 levels were associated with vascular invasion (OR = 3.48, 95 % CI: 1.26-9.59), while normalized DUPAN-2 levels were associated with higher resectability (OR = 0.57, 95 % CI: 0.36-0.90) and lower N-stage (OR = 0.39, 95 % CI: 0.24-0.63) CONCLUSION: Serum DUPAN-2 demonstrates significant potential as a biomarker for diagnosis and prognosis in patients with PC., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Long noncoding RNA (lncRNA) PTTG3P has been demonstrated to participate in the development of hepatocellular carcinoma (HCC) by targeting the mRNA PTTG1. The present study aimed to investigate the diagnostic efficacy of serum lncRNA PTTG3P, mRNA PTTG1 and their combination for the diagnosis and prognosis of HCC. A total of 373 participants were enrolled in the present study, including 73 patients with HCC, 100 patients with chronic hepatitis B (CHB), 100 patients with liver cirrhosis (LC) and 100 healthy controls (HCs). The expression levels of serum RNAs were quantified by reverse transcription‑quantitative PCR. The association between serum lncRNA PTTG3P and clinical characteristics was further analyzed. Receiver operating characteristic (ROC) curve and area under curve (AUC) analyses were performed to estimate the diagnostic ability of serum lncRNA PTTG3P, PTTG1 and their combinations with other biomarkers for HCC. The results revealed that the expression levels of lncRNA PTTG3P and mRNA PTTG1 were markedly increased in the serum of patients with HCC and CHB compared with in the serum of HCs. Additionally, the postoperative levels of lncRNA PTTG3P and mRNA PTTG1 were significantly lower than the preoperative concentrations in 36 paired patients with HCC. Spearman's correlation coefficient analysis showed that serum lncRNA PTTG3P was correlated with aspartate transaminase (AST). ROC analysis showed that both lncRNA PTTG3P and mRNA PTTG1 had a significant predictive value for HCC. The AUC values of lncRNA PTTG3P and mRNA PTTG1 alone were 0.636 and 0.634, respectively. Furthermore, combining lncRNA PTTG3P, mRNA PTTG1, α‑fetoprotein (AFP), alanine aminotransferase (ALT), AST, γ‑glutamyl transpeptidase (GGT) and alkaline phosphatase (ALP) significantly increased the AUC value. The best performance was the combination of PTTG3P, PTTG1, AFP, ALT, AST, GGT and ALP with an AUC of 0.959, a sensitivity of 90.4% and a specificity of 98.0%. In conclusion, the combination of serum lncRNA PTTG3P, mRNA PTTG1 and AFP appeared to be a noninvasive biomarker with comparatively high specificity and sensitivity for the diagnosis of HCC.

Endometrial cancer (EC) is the most prevalent cancer within the female reproductive system in developed countries. Despite its high incidence, there is currently no established laboratory screening test for EC, making early detection challenging. This study introduces an innovative, minimally invasive, and cost-effective method utilizing three-dimensional fluorescence analysis combined with machine learning algorithms to enhance early EC detection. Intrinsic fluorescence of blood serum samples was measured using a luminescence spectrophotometer, which captured fluorescence spectra as synchronous excitation spectra and visualized them through wavelength contour matrices. The spectral data were processed using machine learning algorithms, including Random Forest (RF), Logistic Regression (LR), Support Vector Machine (SVM), and Stochastic Gradient Descent (SGD), along with exploratory techniques such as Principal Component Analysis (PCA) and Partial Least Squares Discriminant Analysis (PLS-DA). Fluorescence ratios R300/330 and R360/490, indicative of altered tryptophan metabolism and redox state changes, were identified as fluorescent spectral markers and represent key metabolic biomarkers. These ratios demonstrated high diagnostic efficacy with AUC values of 0.88 and 0.91, respectively. Among the ML algorithms, LR and RF exhibited high sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV), showing significant promise for clinical application. After optimization, LR achieved a sensitivity of 0.94, specificity of 0.89, and an impressive AUC value of 0.94. The application of this novel approach in laboratory diagnostics has the potential to significantly enhance early detection and improve prognosis for EC patients., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Purpose: Detection of molecular residual disease (MRD) allows for the identification of breast cancer patients at high-risk of recurrence, with the potential that early initiation of treatment at early stages of relapse could improve patient outcomes. The Invitae Personalized Cancer Monitoring™ assay (PCM) is a newly developed next-generation sequencing approach that utilizes up to 50 patient-specific, tumor-informed DNA variants, to detect circulating tumor DNA (ctDNA). The ability of the PCM assay to detect MRD before clinical relapse was evaluated., Methods: The cohort included 61 female patients with high-risk breast cancer who underwent neoadjuvant chemotherapy. Plasma samples were collected before and during neoadjuvant therapy, after surgery and during monitoring. PCM was used to detect ctDNA at each time point., Results: The sensitivity to detect ctDNA in plasma from patients who relapsed during the monitoring phase was 76.9% (10/13). Specificity and positive predictive values were both 100% with all (10/61, 16%) of the patients who had ctDNA detected during the monitoring phase subsequently relapsing. Detection of ctDNA during monitoring was associated with a high-risk of future relapse (HR 37.2, 95% CI 10.5-131.9, p < 0.0001), with a median lead-time from ctDNA detection to clinical relapse of 11.7 months., Conclusion: PCM detected ctDNA in patients who relapsed with a long lead-time over clinical relapse, shows strong association with relapse-free survival and may be used to identify patients at high-risk for relapse, allowing for earlier intervention., Competing Interests: Declarations. Competing interests: Robert Daber, Benjamin Hubert, Peter DeFord, David Wooten, Jianhua Zhao, and Rachel E. Ellsworth are current employees of Labcorp Genetics, Inc. Robert Daber, Benjamin Hubert, Chiharu Graybill, Peter DeFord, David Wooten, Jianhua Zhao, Rachel E. Ellsworth and W. Michael Korn are former employees and shareholders of Invitae Corp. Ethical approval: This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Research Ethics Committee ref. no. 11/EE/0063. Consent to participate: Written informed consent was obtained from all participants., (© 2024. The Author(s).)

Objectives: Developing a nomogram integrating MR elastography (MRE)-based tumour stiffness and contrast-enhanced MRI in identifying cytokeratin 19 (CK19) status of hepatocellular carcinoma (HCC) preoperatively., Methods: One hundred twenty CK19-negative HCC and 39 CK19-positive HCC patients undergoing curative resection were prospectively evaluated. All received MRE and contrast-enhanced MRI. Clinical and MRI tumour features were compared. Univariate and multivariate logistic regression analyses identified independent predictors for CK19 status. Receiver operating characteristic curve analysis evaluated diagnostic performance. A nomogram was established with calibration and decision curve analysis., Results: Multivariate analysis revealed serum alpha fetoprotein (AFP) level (P < 0.001), targetoid appearance (P = 0.007), and tumour stiffness (P = 0.011) as independent significant variables for CK19-positive HCC. The area under the curve for tumour stiffness was 0.729 (95% confidence interval [CI] 0.653, 0.796). Combining these features, a nomogram-based model achieved an area under the curve value of 0.844 (95% CI 0.778, 0.897), with sensitivity, specificity, and accuracy of 76.92%, 85.00%, and 83.02%, respectively. Calibration and decision curve analyses demonstrated good agreement and optimal net benefit., Conclusions: MRE-measured tumour stiffness aids in predicting CK19 status in HCC. The combined nomogram incorporating tumour stiffness, targetoid appearance, and AFP provides a reliable biomarker for CK19-positive HCC., Advances in Knowledge: MRE-measured tumour stiffness can be used to predict CK19 status in HCC. The nomogram, which integrates tumour stiffness, targetoid appearance, and AFP levels, has shown improved diagnostic performance. It offers a comprehensive preoperative tool for clinical decision-making, further advancing personalized treatment strategies in HCC management., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Institute of Radiology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objective: Ovarian cancer remains a leading cause of cancer-related deaths in women. Early detection improves prognosis, but current diagnostic tools still need improvement. We aimed to identify high-risk patient profiles for ovarian cancer using cluster analysis of age and tumor marker data., Material and Methods: A secondary dataset analysis was conducted using unsupervised learning techniques. Data were from a University Hospital, originally collected between July 2011 and July 2018 in Taiwan. In total, 349 women diagnosed with ovarian masses, including both benign and malignant tumors, were included in this analysis. The median age was 45 years, and 49 % were diagnosed with ovarian cancer in pathology. We used a hierarchical clustering algorithm to find groups of patients with similar features., Results: Two clusters were identified (N = 204 and 145), with a high-risk cluster (66.2 % malignancy) characterized by significantly older age, higher CA125, HE4, CEA, and AFP levels, and a lower CA19-9 level than the low-risk cluster (24.8 % malignancy). The assessment of clustering stability and internal validity yielded a figure of merit score of 0.970 and a silhouette coefficient of 0.524. A classification model using age, CA125, HE4, and CA19-9 demonstrated high accuracy (89.4 %), sensitivity (94.5 %), specificity (83.7 %), and a large area under the curve (89.1 %) for the risk stratification., Conclusion: Integrating tumor markers with patient demographics improved the differentiation between benign and malignant ovarian masses. This approach can help clinicians prioritize high-risk patients for further diagnostic evaluation and reduce unnecessary invasive procedures for low-risk patients., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Background: AminoIndex™ Cancer Screening (AICS breast) was developed as a breast cancer screening test using multivariate analysis of plasma free amino acid (PFAA) profiles. This study investigated the relationship between the AICS breast rank and breast density on mammography (MMG) for the detection of breast cancer., Materials and Methods: MMG and blood samples were obtained preoperatively from 224 patients with breast cancer who did not receive neoadjuvant chemotherapy between 2017 and 2019. PFAA concentration was measured using liquid chromatography-mass spectrometry, and the AICS breast and AICS ranks were calculated. Detection rates were compared between MMG (categories 3-5) and AICS breasts (ranks B and C) according to breast density., Results: Breast density was classified as extremely dense in 9.4%, heterogeneously dense in 48.2%, scattered in 29.9%, and fatty in 12.5% of patients. Dense breasts (extremely dense and heterogeneously dense) represented 57.6%. The overall detection rate by MMG was 82.6% and significantly lower in patients with dense breasts (74.4%) compared to non-dense breasts (93.7%). The overall detection rate by AICS breast was 50.0%, with no difference between patients with dense breasts (45.7%) and those with non-dense breasts (55.8%). The combination of MMG and AICS breast increased the detection rate to 91.5% overall, 88.3% in patients with dense breasts, and 95.8% in those with non-dense breasts., Conclusion: This study demonstrated that the detection rate of AICS breast was not associated with breast density, unlike MMG. Adding AICS breast to MMG may be beneficial for breast cancer screening in patients with dense breasts., Competing Interests: Disclosure The authors report no proprietary or commercial interests in any of the products or concepts mentioned in this article., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Aims: To enhance ovarian tumor diagnosis beyond conventional methods, this study explored combining diffusion-weighted magnetic resonance imaging (DWI-MRI) and serum biomarkers (Mucin 1 [MUC1], MUC13, and MUC16) for distinguishing borderline from malignant epithelial ovarian tumors., Methods: A total of 126 patients, including 71 diagnosed with borderline (BEOTs) and 55 with malignant epithelial ovarian tumors (MEOTs), underwent preoperative DWI-MRI. Region of interest (ROI) was manually drawn along the solid component's boundary of the largest tumor, focusing on areas with potentially the lowest apparent diffusion coefficient (ADC). For entirely cystic tumors, a free-form ROI enclosed the maximum number of septa while targeting the lowest ADC. Serum biomarkers were determined using enzyme-linked immunosorbent assay., Results: Basic morphological traits proved inadequate for malignancy diagnosis, warranting this investigation. BEOTs had an ADC mean of (1.670 ± 0.250) × 10 3 mm 2 /s, while MEOTs had a lower ADC mean of (1.332 ± 0.481) × 10 3 mm 2 /s, with a sensitivity of 63.6% and specificity of 90.1%. Median MUC1 (167.0 U/mL vs. 87.3 U/mL), MUC13 (12.44 ng/mL vs. 7.77 ng/mL), and MUC16 (180.6 U/mL vs. 36.1 U/mL) levels were higher in MEOTs patients. The biomarker performance was: MUC1, sensitivity 50.9%, specificity 100%; MUC13, sensitivity 56.4%, specificity 78.9%; MUC16, sensitivity 83.64%, specificity 100%. Combining serum biomarkers and ADC mean resulted in a sensitivity of 96.4% and specificity of 100%., Conclusion: The integration of DWI-MRI with serum biomarkers (MUC1, MUC13, and MUC16) achieves exceptional diagnostic accuracy, offering a powerful tool for the precise differentiation between borderline and malignant epithelial ovarian tumors., (© 2024 The Authors. Asia‐Pacific Journal of Clinical Oncology published by John Wiley & Sons Australia, Ltd.)

Background: This study aimed to assess the significance of elevated carbohydrate antigen (CA) 19-9 in postoperative surveillance of extrahepatic bile duct cancer and to identify short-term recurrence predictors., Methods: This retrospective study included patients with elevated CA 19-9 post-curative surgery. Patients were categorized into positive and negative CT groups based on the detection of recurrence at CA 19-9 elevation. Short-term recurrence was defined as recurrence within 6 months in the negative CT group. We identified the factors associated with short-term recurrence and devised a predictive nomogram., Results: Among the 190 patients, 91 (47.9 %) exhibited tumor recurrence with CA 19-9 elevation (CT-positive group), whereas 99 (52.1 %) showed no recurrence (CT-negative group). In the CT-negative group (n = 99), 22 (22.2 %) experienced short-term tumor recurrence within 6 months. Preoperative CA 19-9 (odds ratio [OR]: 1.5, p = 0.016), postoperative CA 19-9 (OR: 1.9, p = 0.047), adjuvant treatment (OR: 3.5, p = 0.032), and the absence of inflammation (OR: 3.5, p = 0.045) were predictors of short-term recurrence. The area under the curve of the nomogram was 0.80 (95 % CI: 0.69-0.90)., Conclusion: Despite elevated CA 19-9 levels, approximately 50 % of patients exhibited no recurrence during postoperative surveillance for extrahepatic bile duct cancer. Factors influencing short-term recurrence encompass pre- and postoperative CA 19-9, adjuvant treatment, and inflammatory status., (Copyright © 2024 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)