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Glioblastoma is a highly aggressive neoplasm and the most common primary malignant brain tumor. Endothelial tissue plays a critical role in glioblastoma growth and progression, facilitating angiogenesis, cellular communication, and tumorigenesis. In this review, we present an up-to-date and comprehensive summary of the role of endothelial cells in glioblastomas, along with an overview of recent developments in glioblastoma therapies and tumor endothelial marker identification.

Exosomes are critical tumor biomarkers, which can be detected by label‐free sensing of plasmonic metasurfaces with expensive antibody functionalization. Due to their low cost and small size, aptamers should be promising to replace antibodies in plasmonic metasensing of exosomes. However, research on aptamer‐based plasmonic metasensing of exosomes is still unexplored. Here, the optical near‐field sensing mechanism of aptamer‐based plasmonic metasurface (APM) is investigated. Based on the study of the evanescent field of APM, using thiol‐modified aptamer boosts the utilization rate of resonance wavelength shift from 27.5% to 83.3% compared to biotinylated aptamers, attributed to a significant reduction in the near‐field occupation of the biofunction layer. Moreover, APM biosensors effectively detect clinical serum exosomes for breast cancer (BC) diagnosis and classification. The receiver operating characteristic analysis shows an area under the curve of 99.3% for APM diagnosis, surpassing the 79.1% for hematological tests of the conventional BC biomarker CA153. The results also indicate that APM biosensors can be a noninvasive tool for molecular classification of BC with great distinguishment of P < 0.0001. The research demonstrates that APM biosensors are enabling a reliable and convenient platform to facilitate clinical hematological tests of exosomes for auxiliary diagnosis of cancer. [ABSTRACT FROM AUTHOR]

Introduction: Anti-p53 antibody (p53Ab) is useful for monitoring colorectal cancer (CRC) recurrence. We retrospectively analyzed the clinical impact of p53Ab ratio (p53R) before and after surgery to predict recurrence in patients with CRC. Methods: In total, 1,223 patients with stage I–III CRC who underwent curative surgery between January 2005 and December 2019 were enrolled in this retrospective study. In patients with elevated p53Ab levels, p53R was calculated by measuring p53Ab levels within 1 month preoperatively and 3 months postoperatively. The optimal p53R level was determined, and its relationship with clinicopathological factors and prognosis was examined. We also evaluated the efficacy of the combination of p53R and preoperative carcinoembryonic antigen (CEA) values. Results: Overall, 341 patients (27.9%) showed elevated p53Ab levels. Preoperative p53Ab levels were significantly associated with tumor location, lymphatic invasion, and venous invasion. The p53R level was significantly higher in patients with recurrent disease. Patients with high p53R levels had significantly shorter relapse-free survival than those with low p53R levels (p < 0.001). When p53R was combined with preoperative CEA values, specificity improved to 0.97, with an accuracy of 0.88. Conclusion: In patients with CRC and elevated preoperative p53Ab levels, p53R expression may be prognostically useful after radical resection. Furthermore, the combination of p53R and preoperative CEA levels may be useful for postoperative follow-ups. [ABSTRACT FROM AUTHOR]

Copyright of Baghdad Science Journal is the property of Republic of Iraq Ministry of Higher Education & Scientific Research (MOHESR) and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Independent and valid prognostic predictors for locally advanced gastric cancer (LAGC) patients with non-elevated serum tumor markers (Triple-negative: CA199 < 37U/ml, CEA < 5 µg/ml and CA125 < 35U/ml) before and after neoadjuvant chemotherapy (NACT) remain unclear. Methods: A total of 352 LAGC patients treated with NACT(NLAGC) from two centers were included. Of the 156 were Triple-negative patients. CA72-4 trajectory groupings was defined as longitudinal changes in CA72-4 levels before and after NACT to identify different potential subgroups and to compare recurrence-free survival (RFS) and overall survival (OS) among subgroups. The predictive performance of the nomogram-trajectory was evaluated using the area under the receiver operating characteristic curve(AUC), decision curve analysis, and C-index. Results: In the Triple-negative patients, the Stable group had significantly worse 3-year OS than the Normal, Elevated, and Descend groups(3-year OS: 53.9% vs. 77.9% vs. 73.5% vs. 87.7%;P = 0.002). Cox multivariate analysis showed that CA72-4 trajectory groupings (Stable group: HR:3.442, 95%CI[1.574–7.528], P = 0.002) was an independent prognostic risk factor. In addition, the C-index and AUC values based on the nomogram-trajectory were significantly higher than those of ypTNM staging (C-index: 0.788 vs. 0.719,P < 0.001;AUC: 0.800 vs. 0.667,P < 0.001). Furthermore, The survival analysis revealed that the 3-year OS of the Low-Risk group of nomogram scores was significantly better than that of the High-Risk group(3-year OS:84.7% vs. 29.1%). And the Low-Risk group had the lower cumulative risk of recurrence (P < 0.001). Conclusion: The CA72-4 trajectory groupings were an independent prognostic factor for NLAGC Triple-negative patients. The predictive efficacy of the Nomogram-trajectory was significantly better than the ypTNM. [ABSTRACT FROM AUTHOR]

CA 15-3 and CEA are tumor markers used in routine clinical care for breast cancer and colorectal cancer, among others. Current measurement procedures (MP) for these tumor markers are considered to be insufficiently harmonized. This study investigated the achievable harmonization for CA 15-3 and CEA by using an in silico simulation of external quality assessment (EQA) data from multiple EQA programs using patient-pool based samples.CA 15-3 and CEA data from SKML (2021), UK NEQAS (2020–2021) and KEQAS (2020–2021) were used. A harmonization protocol was defined in which MPs that were considered equivalent were used to value assign EQA samples, and recalibration was only required if the MP had a bias of >5 % with value assigned EQA. Harmonization status was assessed by determining the mean level of agreement and residual variation by CV (%).Only MPs from Abbott, Beckman, Roche and Siemens were available in all EQA programs. For CA 15-3, recalibration was proposed for Beckman MP only and for CEA, recalibration was proposed for Siemens MP only. When the harmonization procedures were applied, for CA 15-3 the pre-harmonization mean bias range per MP was reduced from −29.28 to 9.86 %, into −0.09–0.12 % after harmonization. For CEA, the mean bias range per MP was reduced from −23.78 to 2.00 % pre-harmonization to −3.13–1.42 % post-harmonization.The present study suggests that a significant improvement in the harmonization status of CA 15-3 and CEA may be achieved by recalibration of a limited number of MPs. [ABSTRACT FROM AUTHOR]

AbstractTo establish age- and sex-specific reference intervals (RIs) for serum tumor markers (AFP, CEA, CA125, CA199, CA153, HE4, CA724, CYFRA21-1, PSA, and NSE) among a cohort of healthy individuals in South China, a retrospective analysis was conducted on 51,353 samples collected from 2015 to 2020, during health assessments at Guangdong Provincial People’s Hospital. The influence of age and gender on serum tumor markers was investigated. New RIs were determined using non-parametric rank-based methods per CLSI EP28-A3C guidelines. Significant differences were detected across age groups for AFP, CEA, CA125, CA199, HE4, CYFRA21-1, PSA, and NSE (p < 0.05). The upper reference limits (URLs) for CA153 and HE4 are significantly lower compared to our current laboratory standards. The URL for CA125 exceeds these limits in individuals under 50 but decreases in those aged 50 and above. For CA199, CEA, and PSA, the URLs are below current standards in individuals younger than 60 but exceed them in those aged 60 and older. Noteworthy elevations were observed in CA724, CYFRA21-1, and NSE levels. Our study establishes age- and sex-specific RIs for ten serum tumor markers among healthy individuals from South China, providing a fundamental resource for the prevention, early detection, and management of tumor-related disorders. [ABSTRACT FROM AUTHOR]

Serum and pleural fluid tumor markers are well-recognized auxiliary diagnostic tools for malignant pleural effusion (MPE). Here, we discuss some pearls and pitfalls regarding the role of tumor markers in MPE management. The following issues are discussed in this article: What is the appropriate clinical scenario for evaluating pleural tumor markers? Which tumor markers should be advocated for diagnosing MPE? Can extremely high levels of tumor markers be employed to establish a diagnosis of MPE? Does the serum-to-pleural fluid ratio of a tumor marker have the same diagnostic efficacy as the measurement of that marker alone in the pleural fluid? Can tumor markers be used to estimate the risk of specific cancers? What should be considered when interpreting the diagnostic accuracy of tumor markers? How should tumor marker studies be performed? We addressed these issues with published works, particularly systematic reviews and meta-analyses. [ABSTRACT FROM AUTHOR]

Tumor markers such as carbohydrate antigen 19-9 (CA19-9) are generally useful in ruling out malignancy of hepatic cysts. The patient was a 72-year-old man who had a ruptured liver cyst in the right liver, which had been noted since he was 67 years old at another hospital. The initial laboratory tests demonstrated elevated CA19-9 (193 784.3 U/mL). We made the diagnosis with a simple ruptured liver cyst from magnetic resonance imaging and cytological examination of ascites, and laparoscopic fenestration with drainage of the abdominal fluid was performed. Pathological diagnosis of the resected wall cyst was non-parasitic simple hepatic cyst with acute inflammation and hemorrhage. The patient's serum levels of CA19-9 were 164.0 U/mL on postoperative day 23. The follow-up abdominal computed tomography scan performed 2 months later did not any finding of tumor. [ABSTRACT FROM AUTHOR]

A highly sensitive surface-enhanced Raman scattering (SERS) biosensor has been developed for the detection of microRNA-21 (miR-21) using an isothermal enzyme-free cascade amplification method involving catalytic hairpin assembly (CHA) and hybridization chain reaction (HCR). The CHA reaction is triggered by the target miR-21, which causes hairpin DNA (C1 and C2) to self-assemble into CHA products. After AgNPs@Capture captures the resulting CHA product, the HCR reaction is started, forming long-stranded DNA on the surface of AgNPs. A strong SERS signal is generated due to the presence of a large amount of the Raman reporter methylene blue (MB) in the vicinity of the SERS "hot spot" on the surface of AgNPs. The monitoring of the SERS signal changes of MB allows for the highly sensitive and specific detection of miR-21. In optimal conditions, the biosensor exhibits a satisfactory linear range and a low detection limit for miR-21 of 42.3 fM. Additionally, this SERS biosensor shows outstanding selectivity and reproducibility. The application of this methodology to clinical blood samples allows for the differentiation of cancer patients from healthy controls. As a result, the CHA-HCR amplification strategy used in this SERS biosensor could be a useful tool for miRNA detection and early cancer screening. [ABSTRACT FROM AUTHOR]

Abstract Background Independent and valid prognostic predictors for locally advanced gastric cancer (LAGC) patients with non-elevated serum tumor markers (Triple-negative: CA199

Purpose: Macrophage migration inhibitory factor (MIF) is an integral cytokine for the modulation of both innate and adaptive immunity and is involved in the pathogenesis of various cancers. However, conflicting findings on the relationship between MIF polymorphisms and breast cancer (BC) have been reported in earlier research. We investigated the clinical value of serum MIF levels and the association between MIF rs1049829 and rs755622 variants with their serum levels and propensity to develop BC. Methods: A total of 133 treatment-naïve Egyptian BC females and 126 apparently healthy controls were matriculated in this case–control study. The serum MIF protein levels were quantified by ELISA, whereas the genotyping was executed utilizing the TaqMan® allelic discrimination assay. Results: A significant increase in the serum MIF level in BC cases was observed in comparison to control subjects (P < 0.0001), with a diagnostic potential to discriminate BC with 92.5% sensitivity and 73.7% specificity at a cut-off value > 9.47 ng/mL. Besides, a significant difference in serum MIF level was observed in BC cases with progesterone receptor (PR) negativity compared to those with PR positivity (P = 0.046). Moreover, a significant association was depicted between the rs1049829 variant of MIF gene and the protective effect against BC meanwhile the rs755622 variant demonstrated no significant link with BC risk. Conclusions: This study revealed that serum MIF levels may be regarded as a promising serum tumor marker for BC. Also, the rs1049829 variant of the MIF gene is considered a protective candidate against BC. [ABSTRACT FROM AUTHOR]

Yuexi Liu,&ast; Qiuying Gu,&ast; Yao Xiao, Xing Wei, Jinlong Wang, Xiaolan Huang, Hua Linghu Department of Gynecology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hua Linghu, Department of Gynecology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People’s Republic of China, Email linghuhua@cqmu.edu.cnPurpose: To evaluate Ki67 expression and prognostic value during neoadjuvant chemotherapy (NACT) in advanced epithelial ovarian cancer (EOC).Patients and Methods: 95 patients with advanced EOC receiving NACT followed by interval debulking surgery (IDS) were available for tissue samples from matched pre- and post-therapy specimens. The expression of Ki-67 was evaluated by immunohistochemistry and classified by percentage of stained cells. The optimal cutoff values of the Ki67 were assessed by receiver operating characteristic analysis. Kaplan-Meier analysis, the Log rank test, and Cox regression analysis were carried out to analyze survival.Results: Post-NACT Ki67 was an independent prognostic factor for recurrence by univariate (HR: 1.8, 95% CI: 1.1– 3.0, P-value: 0.023) and multivariate (HR: 1.88, 95% CI: 1.08– 3.26, P-value: 0.025) analysis. Residual disease > 1cm (HR: 2.69, 95% CI: 1.31– 5.54, P-value: 0.0070) and pre-treatment CA125 ≥ 1432 U/mL (HR: 2.00, 95% CI: 1.13– 3.55, P-value: 0.017) were also independent risk factors for progression-free survival (PFS) in multivariate analysis. Post-NACT Ki67 ≥ 20% was an independent risk factor for PFS, however, baseline Ki67 and Ki67 change did not suggest prognostic significance. In patients with high CA125, the median PFS for patients with high postKi67 (median PFS: 15.0 months, 95% CI: 13.4– 16.6 months) was significantly (P-value: 0.013) poorer compared to patients with low postKi67 (median PFS: 30.0 months, 95% CI: 13.5– 46.5 months).Conclusion: Post-NACT Ki67 ≥ 20% was an independent factor associated with poorer PFS in patients with advanced-stage EOC undergoing NACT followed by IDS. The combination of post-NACT Ki67 and pretreatment CA125 could better identify patients with poorer PFS in NACT-administered patients.Keywords: interval debulking surgery, progression-free survival, overall survival, tumor marker

Abstract Background The aim is to establish and verify reference intervals (RIs) for serum tumor markers for an apparently healthy elderly population in Southwestern China using an indirect method. Methods Data from 35,635 apparently healthy elderly individuals aged 60 years and above were obtained in West China Hospital from April 2020 to December 2021. We utilized the Box-Cox conversion combined with the Tukey method to normalize the data and eliminate outliers. Subgroups are divided according to gender and age to examine the division of RIs. The Z-test was used to compare differences between groups, and 95% distribution RIs were calculated using a nonparametric method. Results In the study, we observed that the RIs for serum ferritin and Des-γ-carboxy prothrombin (DCP) were wider for men, ranging from 64.18 to 865.80 ng/ml and 14.00 to 33.00 mAU/ml, respectively, compared to women, whose ranges were 52.58 to 585.88 ng/ml and 13.00 to 29.00 mAU/ml. For other biomarkers, the overall RIs were established as follows: alpha-fetoprotein (AFP) 0–6.75 ng/ml, carcinoembryonic antigen (CEA) 0–4.85 ng/ml, carbohydrate antigen15-3 (CA15-3) for females 0–22.00 U/ml, carbohydrate antigen19-9 (CA19-9) 0–28.10 U/ml, carbohydrate antigen125 (CA125) 0–20.96 U/ml, cytokeratin 19 fragment (CYFRA21-1) 0–4.66 U/ml, neuron-specific enolase (NSE) 0–19.41 ng/ml, total and free prostate-specific antigens (tPSA and fPSA) for males 0–5.26 ng/ml and 0–1.09 ng/ml. The RIs for all these biomarkers have been validated through our rigorous processes. Conclusion This study preliminarily established 95% RIs for an apparently healthy elderly population in Southwestern China. Using real-world data and an indirect method, simple and reliable RIs for an elderly population can be both established and verified, which are suitable for application in various clinical laboratories.

Abstract Purpose To explore the clinical value of tumor abnormal protein (TAP) in the diagnosis and prognosis evaluation of prostate cancer. Methods This study enrolled a total of 265 patients who underwent prostate biopsy procedures from December 2017. TAP levels were assayed in their blood samples using a validated TAP testing kit. Comprehensive pathological assessments, including Gleason scores, TNM staging, and AJCC prognosis stages, were conducted on prostate cancer patients. Further analysis was carried out to examine the correlation between TAP expression levels and various clinical characteristics. Results A significantly elevated TAP concentration was discerned in prostate cancer patients relative to those with benign prostate hyperplasia. Moreover, a significantly elevated TAP expression was detected in prostate cancer patients with high Gleason score (≥ 8) and advanced stages (III and IV), as compared to those with Gleason scores of 6 and 7 and lower stages (I and II). When diagnosing prostate cancer in gray area of PSA, TAP demonstrated superior diagnostic capabilities over PSA alone, with higher diagnostic sensitivity, specificity and accuracy than fPSA/tPSA ratio. Additionally, post-surgical or hormonal treatment, there was a marked reduction in TAP expression level among prostate cancer patients. Conclusion The assessment of TAP presents itself as a promising tool for early diagnosis and holds potential for sensitivity in monitoring treatment reponse in prostate cancer patients.

Abstract Matrix metalloproteinases (MMPs) had a variety of subtypes, which may be related to tumor invasion and angiogenesis, and the polymorphisms from MMPs have been also associated with the susceptibility to a variety of tumors, including prostate cancer (PCa). However, previous studies have not systematically analyzed the association between MMP and prostate cancer, so we conducted systematic data collection and analyzed to evaluate the relationship among polymorphisms in MMPs and PCa susceptibility. We searched PubMed, Web of Science, Embase and Google Scholar for all papers published up to Apr 3rd, 2023, and systematically analyzed the relationship among MMP1-1607 2G/1G, MMP2-1306 T/C, MMP2-735 T/C, MMP7-181 G/A, MMP9-1562 T/C and PCa susceptibility using multiple comparative models and subgroup analyses. We found that MMP2-1306 T/C polymorphism showed associations with PCa susceptibility, with the Ethnicity subgroup (Asian) being more pronounced. Similarly, MMP9-1562 T/C has also had associations with PCa susceptibility. Our current study found that the polymorphisms of, MMP2-1306 T/C, and MMP9-1562 T/C had strong associations with PCa risk.

Copyright of Journal of China Medical University is the property of Journal of China Medical University Editorial Office and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Sensitive detection of tumor markers is one of the most important safeguards for early diagnosis of cancer, selection of therapeutic strategies and prognostic monitoring. The content of tumor markers in serum is low, usually existing at trace level, and even very few other tumor markers are only on the order of femtograms or picograms per millilitre of serum, and subtle changes in their concentrations are indicative of tumor occurrence, progression and therapeutic efficacy. It is of great clinical significance and has received extensive attention how to achieve sensitive detection of small concentration changes of tumor markers at trace level. Because of its high sensitivity, fast response, easy operation, and miniaturization of the instrument, electrochemical immunosensors have received much attention and made great progress in the study of detecting small concentration changes of tumor markers at trace level. This paper reviews the progress made in catalytic reactions to enhance the performance of electrochemical detection of tumor markers, with special focus on the application of bioenzymes, nano-enzymes, and the use of electrochemical metal catalysts, and also provides an outlook on the problems to be solved. [ABSTRACT FROM AUTHOR]

• To examine the effect of factors on HE4 values in a national representative sample of women in the United States. • Elevated HE4 levels were associated with postmenopausal status, endometriosis, nicotine exposure, and poor renal function. • Decreased HE4 levels was associated with use of oral contraceptives. • This study of samples from 98.5 million non-institutionalized women in the United States confirms variables that affect HE4 levels. Human epididymis protein 4 (HE4) is a tumor marker overexpressed in ovarian cancer and is commonly utilized to aid with diagnosis of an adnexal mass. HE4 levels vary based on pregnancy, age, menopausal status, and tobacco use. The objective of this study was to evaluate population-based data to examine factors that affect HE4 among adult women in the United States and stratify levels of HE4 by demographic and gynecologic factors. A retrospective analysis was conducted using data from 2,480 women aged 20 + who participated in the National Health and Nutrition Examination Survey (2001–2002). From these cross-sectional data, serum HE4 and cotinine, a marker of tobacco exposure, were combined with demographic and interview data. Estimated glomerular filtration rates (eGFR) were based on serum creatinine, age, sex, and race. Other variables of interest included menopausal status, pregnancy, and various gynecologic factors. Summary HE4 data are provided as geometric means with associated 95 % confidence intervals. HE4 levels were independently associated with age, renal function, and nicotine use, all p < 0.001. Pre-menopausal women with a history of endometriosis were found to have elevated HE4 levels compared to those without, p < 0.01; however, we found no such difference among post-menopausal women. Adjusting for age, no differences in HE4 were found based on race/ethnicity, p = 0.29. HE4 levels showed statistically significant associations with income level; however, these were small and clinically irrelevant. This study provides evaluation of HE4 levels among a data set representative of 98.5 million non-institutionalized women in the United States and gives insight into extraneous factors that may influence these levels. [ABSTRACT FROM AUTHOR]

Introduction: Previously we demonstrated that elevated serum CYFRA 21 − 1 is a reliable diagnostic and prognostic biomarker for biliary tract cancers. This study aims to explore the diagnostic performance of bile CYFRA 21 − 1 (bCYFRA 21 − 1) in discriminating malignant biliary obstruction (MBO) caused by cholangiocarcinoma (CCA). Methods: 77 CCA patients ((17 intrahepatic CCA (iCCA), 49 perihilar CCA (pCCA) and 11 distal CCA (dCCA)) and 43 benign patients with biliary obstruction were enrolled. Serum and bile levels of CYFRA 21 − 1, carcinoembryonic antigen (CEA) and carbohydrate antigen 19 − 9 (CA19-9) were quantified. Diagnostic performances of these biomarkers were estimated by receiver operator characteristic curves. Subgroups analysis of these tumor markers among CCA subtypes was performed. Results: High bCYFRA 21 − 1 (cut-off value of 59.25 ng/mL with sensitivity of 0.889 and specificity of 0.750) and high bile to serum ratio of CYFRA 21 − 1 (b/sCYFRA 21 − 1, cut-off value of 31.55 with sensitivity of 0.741 and specificity of 0.778) achieved better diagnostic performance than any other biomarker in discriminating MBO. Subgroup analysis revealed that bCYFRA 21 − 1 was significantly elevated in all CCA subtypes; moreover b/sCYFRA 21 − 1 was upregulated in pCCA and dCCA (the mean b/sCYFRA 21 − 1 of pCCA was highest among CCA subtypes: 57.90, IQR 29.82-112.27). Conclusions: Both high biliary CYFRA 21 − 1 and high bile to serum ratio of CYFRA 21 − 1 were reliable diagnostic biomarkers for MBO caused by CCA. [ABSTRACT FROM AUTHOR]

Purpose: To explore the clinical value of tumor abnormal protein (TAP) in the diagnosis and prognosis evaluation of prostate cancer. Methods: This study enrolled a total of 265 patients who underwent prostate biopsy procedures from December 2017. TAP levels were assayed in their blood samples using a validated TAP testing kit. Comprehensive pathological assessments, including Gleason scores, TNM staging, and AJCC prognosis stages, were conducted on prostate cancer patients. Further analysis was carried out to examine the correlation between TAP expression levels and various clinical characteristics. Results: A significantly elevated TAP concentration was discerned in prostate cancer patients relative to those with benign prostate hyperplasia. Moreover, a significantly elevated TAP expression was detected in prostate cancer patients with high Gleason score (≥ 8) and advanced stages (III and IV), as compared to those with Gleason scores of 6 and 7 and lower stages (I and II). When diagnosing prostate cancer in gray area of PSA, TAP demonstrated superior diagnostic capabilities over PSA alone, with higher diagnostic sensitivity, specificity and accuracy than fPSA/tPSA ratio. Additionally, post-surgical or hormonal treatment, there was a marked reduction in TAP expression level among prostate cancer patients. Conclusion: The assessment of TAP presents itself as a promising tool for early diagnosis and holds potential for sensitivity in monitoring treatment reponse in prostate cancer patients. [ABSTRACT FROM AUTHOR]

Background: The aim is to establish and verify reference intervals (RIs) for serum tumor markers for an apparently healthy elderly population in Southwestern China using an indirect method. Methods: Data from 35,635 apparently healthy elderly individuals aged 60 years and above were obtained in West China Hospital from April 2020 to December 2021. We utilized the Box-Cox conversion combined with the Tukey method to normalize the data and eliminate outliers. Subgroups are divided according to gender and age to examine the division of RIs. The Z-test was used to compare differences between groups, and 95% distribution RIs were calculated using a nonparametric method. Results: In the study, we observed that the RIs for serum ferritin and Des-γ-carboxy prothrombin (DCP) were wider for men, ranging from 64.18 to 865.80 ng/ml and 14.00 to 33.00 mAU/ml, respectively, compared to women, whose ranges were 52.58 to 585.88 ng/ml and 13.00 to 29.00 mAU/ml. For other biomarkers, the overall RIs were established as follows: alpha-fetoprotein (AFP) 0–6.75 ng/ml, carcinoembryonic antigen (CEA) 0–4.85 ng/ml, carbohydrate antigen15-3 (CA15-3) for females 0–22.00 U/ml, carbohydrate antigen19-9 (CA19-9) 0–28.10 U/ml, carbohydrate antigen125 (CA125) 0–20.96 U/ml, cytokeratin 19 fragment (CYFRA21-1) 0–4.66 U/ml, neuron-specific enolase (NSE) 0–19.41 ng/ml, total and free prostate-specific antigens (tPSA and fPSA) for males 0–5.26 ng/ml and 0–1.09 ng/ml. The RIs for all these biomarkers have been validated through our rigorous processes. Conclusion: This study preliminarily established 95% RIs for an apparently healthy elderly population in Southwestern China. Using real-world data and an indirect method, simple and reliable RIs for an elderly population can be both established and verified, which are suitable for application in various clinical laboratories. [ABSTRACT FROM AUTHOR]

Matrix metalloproteinases (MMPs) had a variety of subtypes, which may be related to tumor invasion and angiogenesis, and the polymorphisms from MMPs have been also associated with the susceptibility to a variety of tumors, including prostate cancer (PCa). However, previous studies have not systematically analyzed the association between MMP and prostate cancer, so we conducted systematic data collection and analyzed to evaluate the relationship among polymorphisms in MMPs and PCa susceptibility. We searched PubMed, Web of Science, Embase and Google Scholar for all papers published up to Apr 3rd, 2023, and systematically analyzed the relationship among MMP1-1607 2G/1G, MMP2-1306 T/C, MMP2-735 T/C, MMP7-181 G/A, MMP9-1562 T/C and PCa susceptibility using multiple comparative models and subgroup analyses. We found that MMP2-1306 T/C polymorphism showed associations with PCa susceptibility, with the Ethnicity subgroup (Asian) being more pronounced. Similarly, MMP9-1562 T/C has also had associations with PCa susceptibility. Our current study found that the polymorphisms of, MMP2-1306 T/C, and MMP9-1562 T/C had strong associations with PCa risk. [ABSTRACT FROM AUTHOR]

Background: Different types of inflammatory processes and fibrosis have been implicated in the pathogenesis of interstitial lung disease (ILD), a heterogeneous, diffuse, parenchymal lung disease. Acute exacerbation (AE) of ILD is characterized by significant respiratory deterioration and is associated with high mortality rates. Several serum oncomarkers have been used to determine the prognosis of ILD; however, the prognostic value of serum oncomarker levels in patients with AE-ILD remains unclear. Objective: To evaluate the prognostic value of serum oncomarker levels in patients with AE-ILD and its main subtypes. Design: Retrospective study Methods: The serum levels of 8 oncomarkers in 281 patients hospitalized with AE-ILD at our institution between 2017 and 2022 were retrospectively reviewed. The baseline characteristics and serum oncomarker levels were compared between the survival and non-survival groups of AE-ILD and its main subtypes. Multivariate logistic regression analysis was performed to identify independent prognosis-related markers, and the best prognostic predictor was analyzed using receiver operating characteristic curve (ROC) analysis. Result: Idiopathic pulmonary fibrosis (IPF; n = 65), idiopathic nonspecific interstitial pneumonia (iNSIP; n = 26), and connective tissue disease-associated interstitial lung disease (CTD-ILD; n = 161) were the three main subtypes of ILD. The in-hospital mortality rate among patients with AE-ILD was 21%. The serum oncomarker levels of most patients with AE-ILD and its main subtypes in the non-survival group were higher than those in the survival group. Multivariate analysis revealed that ferritin and cytokeratin 19 fragments (CYFRA21-1) were independent prognostic risk factors for patients hospitalized with AE-ILD or AE-CTD-ILD. CYFRA21-1 was identified as an independent prognostic risk factor for patients hospitalized with AE-IPF or AE-iNSIP. Conclusion: CYFRA21-1 may be a viable biomarker for predicting the prognosis of patients with AE-ILD, regardless of the underlying subtype of ILD. Ferritin has a prognostic value in patients with AE-ILD or AE-CTD-ILD. [ABSTRACT FROM AUTHOR]

Aim: To predict the prognosis of gastric cancer patients with triple-negative tumor markers. Materials & methods: Prognostic factors of the nomogram were identified through univariate and multivariate Cox regression analyses. Calibration and receiver operating characteristic curves were used to assess accuracy. Decision curve analysis and concordance indexes were utilized to compare the nomogram with the pathological tumor, node, metastasis stage. Results: A nomogram incorporating log odds of positive lymph nodes, tumor size and lymphocyte-to-monocyte ratio was constructed. The calibration and receiver operating characteristic curves (area under the curve >0.85) showed high accuracy in predicting overall survival. The concordance indexes (0.832 vs 0.760; p < 0.001) and decision curve analysis demonstrated that the nomogram was superior to the pathological tumor, node, metastasis stage. Conclusion: A prediction and risk stratification nomogram has been developed and validated for gastric cancer patients with triple-negative tumor markers. [ABSTRACT FROM AUTHOR]

Background: Autoantibodies targeting tumor-associated antigens (TAAbs) have emerged as promising biomarkers for early cancer detection. This research aimed to assess the diagnostic capacity of anti-BIRC5 autoantibody in detecting AFP-negative hepatocellular carcinoma (ANHCC). Methods: This research was carried out in three stages (discovery phase, validation phase, and evaluation phase) and included a total of 744 participants. Firstly, the anti-BIRC5 autoantibody was discovered using protein microarray, exhibiting a higher positive rate in ANHCC samples (ANHCCs) compared to normal control samples (NCs). Secondly, the anti-BIRC5 autoantibody was validated through enzyme-linked immunosorbent assay (ELISA) in 85 ANHCCs and 85 NCs from two clinical centers (Zhengzhou and Nanchang). Lastly, the diagnostic usefulness of the anti-BIRC5 autoantibody for hepatocellular carcinoma (HCC) was evaluated by ELISA in a cohort consisting of an additional 149 AFP-positive hepatocellular carcinoma samples (APHCCs), 95 ANHCCs and 244 NCs. The association of elevated autoantibody to high expression of BIRC5 in HCC was further explored by the database from prognosis, immune infiltration, DNA methylation, and gene mutation level. Results: In the validation phase, the area under the ROC curve (AUC) of anti-BIRC5 autoantibody to distinguish ANHCCs from NCs in Zhengzhou and Nanchang centers was 0.733 and 0.745, respectively. In the evaluation phase, the AUCs of anti-BIRC5 autoantibody for identifying ANHCCs and HCCs from NCs were 0.738 and 0.726, respectively. Furthermore, when combined with AFP, the AUC for identifying HCCs from NCs increased to 0.914 with a sensitivity of 77.5% and specificity of 91.8%. High expression of BIRC5 gene is not only correlated with poor prognosis of HCCs, but also significantly associated with infiltration of immune cells, DNA methylation, and gene mutation. Conclusion: The findings suggest that the anti-BIRC5 autoantibody could serve as a potential biomarker for ANHCC, in addition to its supplementary role alongside AFP in the diagnosis of HCC. Next, we can carry out specific verification and explore the function of anti-BIRC5 autoantibody in the occurrence and development of HCC. [ABSTRACT FROM AUTHOR]

Sclerosing stromal tumors are a rare type of ovarian tumor in the category of sex cord stromal tumors, which arise from the ovarian connective tissue. This report concerns a case of a sclerosing stromal tumor in a 19-year-old nulliparous woman who presented with the chief complaints of menstrual irregularities and dyspareunia. Preoperative imaging revealed a complex right adnexal mass with blood flow and without associated ascites. Tumor markers were all normal except lactate dehydrogenase, which was elevated. The elevated lactate dehydrogenase, in combination with patient age and menstrual irregularities, initially misdirected the clinicians toward suspicion for dysgerminoma or other malignant germ cell tumor of the ovary. Clinicians should beware of excluding the diagnosis of sex cord stromal tumor on the differential in a young person with an adnexal mass and elevated lactate dehydrogenase.

Abstract Objectives In comparison to the subjects without diabetes, a greater concentration of serum carbohydrate antigen 19 − 9 (CA 19 − 9) was observed in the subjects with diabetes. Nevertheless, since the occurrence of abnormal CA 19 − 9 is not widespread among the whole diabetic population, this phenomenon has not attracted enough attention. The prevalence of abnormal CA 19 − 9 in hospitalized patients with diabetes was the focus of our research. Method A total of 385 subjects with diabetes and 200 controls were enrolled and all had been tested the CA19-9 levels. Cases of cancers were excluded through examination and followup for 1 year. Results We found that the rate of patients with abnormal CA19-9 level was 8.3%. The rate of patients with abnormal CA19-9 level was 14.0% in the HbA1c ≥ 9% group, and 3.0% in the HbA1c

This study aimed to investigate the efficacy of thymosin α1 combined with XELOX in improving immune function and reducing serum tumor markers in patients with colorectal cancer (CRC) after radical surgery. A total of 180 patients who underwent radical surgery for CRC were divided into two groups: an observation group (n = 94) receiving thymosin α1 in combination with XELOX and a control group (n = 86) receiving XELOX alone. Immune function, inflammatory factor levels, serum tumor markers, and quality of life were assessed before and after treatment. Adverse reactions and recurrence rates were compared between the two groups in 1 and 3 years. Following therapy, there was a notable increase in the levels of CD3+, CD4+, and CD4+/CD8+ in all cohorts, particularly in the observation cohort, when compared to pre-therapy levels. Conversely, CD8+ levels decreased across all cohorts, especially in the observation cohort. Additionally, there was an increase in the levels of IL-2 and IFN-γ in the observation cohort, compared to both pre-therapy and control cohort levels, while IL-6 levels decreased. The presence of CEA, CA242, and CA724 reduced significantly across all cohorts following post-therapy, particularly in the observation cohort. Post-therapy, there was a significant increase in the scoring for role, cognitive, social, emotional, and somatic functions in all cohorts, with the most significant improvement observed in the observation cohort. There were no significant differences in the incidence of side effects across cohorts, while neutropenia events were significantly lower in the observation cohort (32.98%) compared to the control cohort (48.84%). The 12-month recurrence rate showed no statistical significance across cohorts, while the observation cohort had a significantly lower three-year recurrence rate (24.47%) compared to the control cohort (59.30%). Thymosin α1 combined with XELOX is effective in improving immune function, reducing serum tumor markers, and minimizing recurrence in CRC patients after radical surgery. This combination therapy may be a promising new direction for the treatment of CRC.

Abstract Background It is difficult to predict gene mutations individually based on clinical background alone. Tumor markers may help to predict each gene mutation. Identifying tumor markers that can predict gene mutation will facilitate timely genetic testing and intervention. Methods We selected 134 cases of advanced or recurrent ALK‐positive and 172 cases of advanced or recurrent EGFR‐positive lung cancer from our clinical database. The cutoff values for the tumor markers were defined as 5.0 ng/mL or higher for carcinoembryonic antigen (CEA) and 3.5 ng/mL or higher for soluble fragment of cytokeratin 19 (CYFRA21‐1) in accordance with the institutional standards. A positive CYFRA21‐1:CEA ratio was defined as 0.7 or higher. Results The CEA‐positivity rate was 49% for ALK‐positive lung cancers and 73% for EGFR‐positive lung cancers, which was significantly different (p

Abstract Purpose The NY‐ESO‐1 antigen is highly immunogenic and often spontaneously induces an immune response in patients with cancer. We conducted a large‐scale multicenter cohort study to investigate the utility of serum NY‐ESO‐1 and p53 antibodies as predictive markers for the postoperative recurrence of gastric cancer. Here, we examined the usefulness of pre‐treatment NY‐ESO‐1 and p53 antibodies as tumor markers for the diagnosis of gastric cancer in combination with carcinoembryonic antigen (CEA) and carbohydrate antigen 19‐9 (CA19‐9). Methods A total of 1031 patients with cT3‐4 gastric cancer were enrolled in the study. NY‐ESO‐1 and p53 antibodies were assessed prior to treatment. The positivity of NY‐ESO‐1 and p53 antibodies, CEA, and CA19‐9 was evaluated before treatment. Results Serum NY‐ESO‐1 and p53 antibodies were positive in 12.6% and 18.1% of the patients, respectively. Positive NY‐ESO‐1 antibody response was correlated with male gender, higher cStage, and upper tumor location. However, a positive p53 antibody response was not associated with tumor factors. The combination of NY‐ESO‐1 or p53 antibody response with CEA and CA19‐9, or the 4‐factors, was positive in 45.1%, 49.6%, and 53.8% of patients, respectively. Moreover, the 4‐factor combination was able to detect >60% of cStage III‐IV diseases, which was 14% higher than that with the combination of CEA and CA19‐9. Conclusion The combination of NY‐ESO‐1 and p53 antibody responses to CEA and CA19‐9 increases the diagnostic accuracy of gastric cancer. Serum NY‐ESO‐1 and p53 antibodies may be useful tumor markers for gastric cancer.

This study aimed to investigate the expression and clinical significance of syncytin-1 in the serum exosomes of hepatocellular carcinoma (HCC) patients. Serum samples were collected from 61 patients with newly diagnosed HCC and 61 healthy individuals. Exosomes were extracted from serum samples and identified using transmission electron microscopy and Western blot. The relative expression levels of syncytin-1 in exosomes were determined by real-time quantitative PCR. The protein expression levels of alpha-fetoprotein and syncytin-1 in HCC patients were detected using enzyme-linked immunosorbent assay (ELISA). Statistical analysis was performed to evaluate the sensitivity and specificity of serum exosomal syncytin-1 in diagnosing HCC. The relationships between syncytin-1 expression and clinical pathological features were analyzed using receiver operating characteristic curve analysis. The results showed that the expression level of syncytin-1 in the serum of patients with newly diagnosed HCC was significantly higher than that in the normal control group (P < 0.0001). Using pathological diagnosis as the gold standard, the sensitivity and specificity of syncytin-1 for the auxiliary diagnosis of HCC were 91.3% and 75.5%, respectively, which were significantly higher than those of alpha-fetoprotein (P < 0.0001). The relative expression level of serum exosomal syncytin-1 was significantly associated with lymph node metastasis, degree of differentiation, and CNLC staging of HCC patients (P < 0.05). In conclusion, syncytin-1 in serum exosomes has high sensitivity and specificity for diagnosing HCC and can serve as a novel tumor marker for early screening, detection, and staging of HCC.

Simple Summary: Circulating tumor cells (CTCs) are cancer cells released from the primary tumor into the bloodstream, and contain cancer stem cells. The present study demonstrates the significance of a specific variant, CD44v9, in CTCs, and its combined effects with preoperative carcinoembryonic antigen (CEA) values on the prognosis of colorectal cancer (CRC). Analysis of the serum CEA levels and the expression of CD44v9 mRNA in CTCs, followed by evaluation of their association with clinicopathological factors, showed the association of CD44v9 mRNA with liver metastasis. Furthermore, patients with CD44v9-positive CTCs showed a poorer prognosis than those with CD44v9-negative CTCs. Combining CD44v9 mRNA expression with CEA values provided more detailed prognostic information. These results suggest that CD44v9 mRNA expression in CTCs, alongside CEA levels, could serve as a valuable prognostic marker for CRC, and could potentially lead to the development of more personalized treatment strategies against CRC. Circulating tumor cells (CTCs) are cancer cells released from the primary tumor into the bloodstream, and contain cancer stem cells that influence tumor survival, recurrence, and metastasis. Here, we investigated CD44v9 expression in CTCs and impact of preoperative carcinoembryonic antigen (CEA) levels on colorectal cancer (CRC) prognosis. We analyzed the expression of CD44v9 mRNA in CTCs using reverse transcription-polymerase chain reaction and preoperative CEA levels in blood samples obtained from 300 patients with CRC. Subsequently, we evaluated the association of CD44v9 expression and CEA levels with clinicopathological factors. CD44v9 mRNA was expressed in 31.3% of the patients, and was significantly associated with liver metastasis. Patients with positive CD44v9 expression had a lower 5-year survival rate (62.3%) than those with negative CD44v9 expression (82.8%, p < 0.001). Cox regression analysis identified CD44v9 expression and high CEA levels (≥5 ng/mL) as poor prognostic factors, while negative CD44v9 expression and low CEA levels (<5 ng/mL) were associated with favorable prognosis (hazard ratio = 0.285, p = 0.006). These results suggest that a combination of CD44v9 mRNA expression in CTCs and serum CEA levels could serve as a valuable prognostic marker for CRC, potentially enhancing the accuracy of prognosis predictions. [ABSTRACT FROM AUTHOR]

Background: The serum level of Krebs von den Lungen-6 (sKL-6) is a biomarker of interstitial pneumonia and has been reported to be elevated in patients with cancers. However, there have been few cases of gastric cancer (GC) with elevated sKL-6 that were treated by chemotherapy. We herein report two cases of GC with elevated sKL-6 that were treated with oxaliplatin plus S-1 (SOX) chemotherapy and discussed the resulting changes in sKL-6. Case presentation: The first patient was a 79-year-old woman complaining of loss of appetite. Esophagogastroduodenoscopy (EGD) showed a type-3 tumor in the gastric antrum and biopsy specimens showed adenocarcinoma. Computed tomography (CT) showed multiple liver metastases. sKL-6 was elevated to 1,292 U/ml, but a CT revealed no obvious lesions of the lungs, including interstitial pneumonia. The tumor was diagnosed as GC with liver metastases and elevated sKL-6. Respiratory function data were normal. SOX therapy using oxaliplatin and S-1 was performed. After 3 courses of SOX therapy, CT showed reductions of the liver metastases as well as the primary tumor, and sKL-6 was decreased to 201 U/ml. After the 44 courses, sKL-6 was slightly elevated. Chest CT showed interstitial pneumonia and chemotherapy was stopped. The patient is still alive without any metastasis 72 months later. The second patient was a 69-year-old woman complaining of upper abdominal pain. EGD revealed a type-3 tumor in the gastric antrum showing adenocarcinoma with HER2-positive pathology. CT showed multiple node metastases around the abdominal aorta. sKL-6 was elevated to 2,239 U/ml, but a respiratory function test showed no abnormalities, and CT of the lungs showed no obvious lesions. The tumor was diagnosed as GC with distant node metastases and elevated sKL-6. The patient received SOX therapy combined with trastuzumab. After 6 courses, the size of the primary tumor and multiple node metastases were reduced, and sKL-6 was decreased to 284 U/ml. Conclusions: These two cases suggest that sKL-6 may be important not only as an indicator of interstitial pneumonia in chemotherapeutic courses, but also as a tumor marker in GC patients with multiple metastases. [ABSTRACT FROM AUTHOR]

Background: To examine standardized uptake valuemax of the primary lesion (pSUVmax) and tumor markers (TMs) for clinically predicting distant metastasis in novo lung adenocarcinoma. Methods: The current retrospective observational study examined individuals diagnosed with de novo lung adenocarcinoma at Shanxi Cancer Hospital between February 2015 and December 2019. Results: Totally, 532 de novo lung adenocarcinoma cases were included. They were aged 60.8 ± 9.7 years and comprised 224 women and 268 patients with distant metastasis. The areas under the curves (AUCs) of pSUVmax, lactate dehydrogenase (LDH), carcinoembryonic antigen (CEA), cytokeratin‐19 fragment (CYFRA21‐1), carbohydrate antigen 125 (CA125), and Grade of TMs for predicting distant metastasis were 0.742, 0.601, 0.671, 0.700, 0.736, and 0.745, respectively. The combination of pSUVmax, LDH, CEA, CYFRA21‐1, CA125, and grade of TMs in predicting distant metastasis had an AUC value of 0.816 (95%CI: 0.781–0.851), with sensitivity of 89.2%, specificity of 58.7%, positive predictive value of 73.7%, and negative predictive value of 79.7%, respectively. Conclusions: pSUVmax combined with serum levels of LDH, CEA, CYFRA21‐1, CA125, and the grade of TMs may have good performance in predicting distant metastasis of de novo lung adenocarcinoma. [ABSTRACT FROM AUTHOR]

The purpose of this study was to investigate the diagnostic efficacy of contrast-enhanced ultrasound (CEUS) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) combined with tumor markers alpha-fetoprotein (AFP) and des-γ-carboxyl prothrombin (DCP) for primary hepatic carcinoma (PHC). A total of 70 patients with PHC (PHC group), 42 patients with liver cyst (benign liver disease group (BLDG)) and 30 healthy people (healthy group (HG)) were selected as the research objects. CEUS and DCE-MRI were performed by American GE Vivid E9 color Doppler ultrasound system and Siemens 1.5T magnetic resonance imager, respectively. The levels of AFP and DCP were detected by ABBOTT i2000SR chemiluminescence instrument and enzyme-linked immunoassay (ELISA), respectively. In DCE-MRI examination, the portal phase and prolonged phase were mostly low signal in T1-weighted imaging (T1WI) sequence, and arterial phase was mostly high signal in T2WI sequence. In CEUS, most lesions showed hyper-enhancement in arterial phase, and hypo-enhancement in portal phase and delayed phase. AFP and DCP levels in PHC group were significantly higher than that in BLDG group and HG group. There were statistically significant differences among the three groups. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of combined diagnosis were statistically significant when compared with CEUS, AFP and DCP alone and either AFP or DCP positive. CEUS, DCE-MRI combined with tumor markers AFP and DCP have high sensitivity, specificity and accuracy in the diagnosis of PHC, which can more accurately diagnose the lesion type, provide basis for further treatment, and is worthy of clinical application. [ABSTRACT FROM AUTHOR]

Epidermal growth factor receptor (EGFR) is the most frequently overexpressed receptor histologically exhibited by oral squamous cell carcinoma (OSCC) patients. Aberrated EGFR signaling may lead to recurrence and metastasis, thus laying the foundation of targeted therapy. Deactivating EGFR is likely to prevent downstream signaling thus resulting in apoptosis. Tyrosine kinase inhibitors (TKIs) have come into play to revert aggressiveness of OSCC. We exploited comparative proteomic analyses based on anti‐EGFR potential of varlitinib, using cellular proteomes from treated and untreated groups of oral cancer cells to identify protein players functional during oral carcinogenesis. Following separation by two-dimensional electrophoresis, differentially expressed cellular proteins (varlitinib-treated and untreated cells) were analyzed and later identified using QTOF mass spectrometer. In silico analysis for protein–protein interaction was carried out using STRING. Six differentially expressed proteins were identified as binding immunoglobulin protein (BiP), heat shock protein 7 C (HSP7C), protein disulfide isomerase 1 A (PDIA1), vimentin (VIME), keratin type I cytoskeletal 14 (K1C14), and β-Actin (ACTB). Relative expression of five proteins was found to be downregulated upon varlitinib treatment, whereas only K1C14 was upregulated in treated cells compared to control. Protein network analysis depicts the interaction between BiP, PDIA1, VIME, etc. indicating their role in oral carcinogenesis. Oral cancer cells show proteome shift based on varlitinib treatment compared to corresponding controls. Our data suggest candidature of varlitinib as a potent therapeutic agent and BiP, PDIA1, HSP7C, VIME, and β-Actin as complementary/prognostic markers of OSCC. [ABSTRACT FROM AUTHOR]

Purpose: The NY‐ESO‐1 antigen is highly immunogenic and often spontaneously induces an immune response in patients with cancer. We conducted a large‐scale multicenter cohort study to investigate the utility of serum NY‐ESO‐1 and p53 antibodies as predictive markers for the postoperative recurrence of gastric cancer. Here, we examined the usefulness of pre‐treatment NY‐ESO‐1 and p53 antibodies as tumor markers for the diagnosis of gastric cancer in combination with carcinoembryonic antigen (CEA) and carbohydrate antigen 19‐9 (CA19‐9). Methods: A total of 1031 patients with cT3‐4 gastric cancer were enrolled in the study. NY‐ESO‐1 and p53 antibodies were assessed prior to treatment. The positivity of NY‐ESO‐1 and p53 antibodies, CEA, and CA19‐9 was evaluated before treatment. Results: Serum NY‐ESO‐1 and p53 antibodies were positive in 12.6% and 18.1% of the patients, respectively. Positive NY‐ESO‐1 antibody response was correlated with male gender, higher cStage, and upper tumor location. However, a positive p53 antibody response was not associated with tumor factors. The combination of NY‐ESO‐1 or p53 antibody response with CEA and CA19‐9, or the 4‐factors, was positive in 45.1%, 49.6%, and 53.8% of patients, respectively. Moreover, the 4‐factor combination was able to detect >60% of cStage III‐IV diseases, which was 14% higher than that with the combination of CEA and CA19‐9. Conclusion: The combination of NY‐ESO‐1 and p53 antibody responses to CEA and CA19‐9 increases the diagnostic accuracy of gastric cancer. Serum NY‐ESO‐1 and p53 antibodies may be useful tumor markers for gastric cancer. [ABSTRACT FROM AUTHOR]

To assess the prognostic value of human epididymis protein 4 (HE4) kinetics during and after neoadjuvant chemotherapy (NACT) cycles compared with cancer antigen 125 (CA-125), in predicting the surgical outcomes of interval debulking surgery (IDS) in patients with advanced-stage, high-grade serous ovarian cancer. This retrospective cohort study was conducted at Severance Hospital in Seoul, South Korea and involved 123 women with high-grade serous epithelial ovarian, fallopian tube, or primary peritoneal cancer who were diagnosed between April 2015 and July 2020. Three outcomes were considered: the chemotherapy response score (CRS) by omentum, residual disease after IDS, and recurrence. Other clinical, imaging, and biological parameters at baseline, during NACT cycles, and pre- and postoperative time were collected and analyzed. We observed a substantial and gradual decrease in both CA-125 level (median from 1612 to 85.55 U/mL; p < 0.001) and HE4 level (514.7 to 87.7 pmol/L; p < 0.001) during NACT cycles, while pre-to-postoperative reduction was only significant for HE4 (median from 77.3 to 62.0 pmol/L (p < 0.001)). Of the total patients, 4.1% showed no response to NACT (chemoresistance) and 65.9% had a partial response. Residual disease was observed in 55 (44.7%) patients. Recurrence occurred in 90 patients (73.2%), with a median progression-free survival of 15.28 months. The percent reduction in CA-125 level– but not HE4 – during NACT was significantly associated with CRS (by omentum); the reduction in CA-125 during NACT cycles was higher when the CRS was found to be 3 and 2 (median = 96.4 [IQR = 8.3] and 93.7 [12.2] respectively) compared to score 1 (68.3 [34.1]), and the difference was statistically significant (p = 0.004). However, no significant association was observed between the percent reduction in CA-125 or HE4 levels during NACT and residual disease or recurrence. The normalization of HE4 – but not CA-125 – before surgery was predictive for surgery outcome; that is, an abnormal preop HE4 level was associated with a residual disease risk ratio of 2.72 (95% CI = 1.27–5.79). Monitoring HE4 or CA-125 levels has low prognostic value in patients with advanced-stage, high-grade serous ovarian cancer who are treated with NACT followed by IDS. However, the preoperative level of the HE4 biomarker may be useful in identifying patients at higher risk for suboptimal cytoreductive surgery or who may require more extensive surgery. Further prospective studies are warranted to explore the prognostic utility of eventual combinations of clinical, radiological, and biological parameters, notably by using artificial intelligence-based models. • The reduction of CA125 during NACT cycles–but not HE4– was significantly associated with chemotherapy response score (CRS). • Pre-to-postop reduction in tumor markers level was only significant for HE4. • The normalization of HE4 level – but not CA125 – before surgery was predictive for surgery outcome. • Complete/near-complete CRS (CRS 3) was the only significant factor for recurrence. [ABSTRACT FROM AUTHOR]

Simple Summary: There have been no analyses of tumor budding (TB) in different margin sections and using the fixation method in HNSCC in the literature. The mean TB (TB rel) of all tumor-positive margin sections (n = 443) of the primary tumor was analyzed in an FFPE-fixed tumor from 66 patients with HNSCC, and they were compared with cryo-fixed sections. TB rel correlates significantly with tumor aggressiveness. TB often varies between the different tumor margins of FFPE sections of the same patient, and they differ depending on the fixation method. Our data show that a randomly selected margin section does not reliably reflect the TB, and thus, it cannot predict the prognostic outcome. TB rel could compensate for the differences in TB score analysis. The determination of the TB score in cryo sections seems to be inaccurate compared with analyses in FFPE. The method shown here is cost effective, easy to integrate into a clinical workflow, and seems useful for future studies. Background: Tumor budding (TB) is a histomorphological characteristic of the tumor invasion front and it has an impact on the tumor outcome prediction for head and neck squamous cell carcinoma (HNSCC) aetiopathology. Patients and methods: The average TB score (TB rel) of all tumor-positive marginal sections (n = 443) in the primary tumor was analyzed in the FFPE-fixed tumor slices of 66 patients with HNSCC, and they were compared with cryo-fixed sections. Results: TB rel correlates with tumor aggressiveness (i.e., lymph node metastasis quantity, lymph node ratio, extra capsular growth, Pn1, pV1, grading). The TB scores often vary between the different tumor margins of FFPE sections in the same patient, and in many cases, they differ depending on the fixation method. Conclusion: Our data show that a randomly selected marginal cut cannot reliably mirror the TB score, and thus, they cannot predict the prognostic outcome. However, TB rel could be a tool that compensates for differences in TB score analysis. TB score determination in cryo sections seems to be inaccurate compared with TB determination in FFPE. [ABSTRACT FROM AUTHOR]

Objective: to determine if the tumor marker squamous cell carcinoma antigen (SCC‐Ag) observed over time may contribute to the early detection of recurrence, metastasis, and second primary tumors in the follow‐up of patients with head and neck squamous cell carcinoma (HNSCC). Study Design: A retrospective analysis of patients with HNSCC and at least one SCC‐Ag measurement was conducted. Hazard ratios (HRs) were used to determine the correlation between SCC‐Ag and an event. Setting: patients with HNSCC, treated in the Antoni van Leeuwenhoek Hospital in The Netherlands between 2010 and 2020 were used for the analysis. Methods: Data from 789 patients were used on event‐free survival (EFS) with time‐dependent Cox models. In addition to current (most recent) SCC‐Ag (also dichotomized into high and low as done for clinical practice), average SCC‐Ag and change between SCC‐Ag measurements (delta SCC‐Ag) were considered, using restricted cubic splines to explore nonlinear relationships. Results: Dichotomized SCC‐Ag values (HR = 3.01, 95% confidence interval [CI]: 2.17‐4.18) and the delta SCC‐Ag (HR = 1.15, 95% CI: 1.07‐1.22) predicted EFS better than models using the cumulative average or current value of SCC‐Ag, also after adjusting for tumor site, stage, age, and gender. A strong association was observed when using delta SCC‐Ag as a linear predictor in the subgroup of oropharynx patients (HR = 4.88, 95% CI: 2.71‐8.79). Conclusion: Dichotomized and delta SCC‐Ag values can be important markers for EFS, during the follow‐up of patients treated for HNSCC. These results were more evident in patients with oropharyngeal cancer. [ABSTRACT FROM AUTHOR]

BackgroundTumor markers are established laboratory tools that help to diagnose, estimate prognosis, and monitor the course of cancer. For meaningful decision-making in patient care, it is essential that methods and analytical platforms demonstrate high sensitivity, specificity, precision, and comparability. Regular participation at external quality assessment (EQA) schemes is mandatory for laboratories. Here, a longitudinal evaluation of EQA data was performed to assess the performance of tumor marker assays over time.MethodsLongitudinal data of the cancer antigens (CA) 15-3 (n = 5,492), CA 19-9 (n = 6,802), and CA 125 (n = 5,362) from 14 INSTAND EQAs conducted between 2019 and 2023 were evaluated. A median of 197, 244 and 191 laboratories participated at the EQAs for CA 15-3, CA 19-9 and CA 125, respectively. Data evaluation encompasses intra- and inter-manufacturer specific variations over time, assay precision, and adherence to the EQA limits of ±24% for CA 15-3, ±27% for CA 19–9 and ±36% for CA 125.ResultsThe study showed median manufacturer-dependent differences of up to 107% for CA 15-3, 99% for CA 125, and even 549% for CA 19-9 between the highest and the lowest methods over the studied period. Regarding the normalized median of all methods, the values of the most deviant methods were 0.42 for CA 15-3, 7.61 for CA 19-9, and 1.82 for CA 125. Intra-manufacturer variability was generally low, with median coefficients of variation (CV) below 10%. As the methods were evaluated according to method-specific consensus values, most participants passed the EQAs within the acceptance criteria. When the criteria were consistently set at 24%, the central 90% of participants passed the EQAs in 78.6%–100% for CA 15-3 (with exception of AX), 89.3%–100% for CA 125, and 64.3%–100% for CA 19-9.ConclusionWhile intra-method precision of most analytical platforms is acceptable for all three tumor markers, considerable inter-method variability was observed over the whole studied period demonstrating the necessity for better standardization and harmonization of the methods, development of international reference materials, and comprehensive commutability studies with patient samples.

Background Autoantibodies targeting tumor-associated antigens (TAAbs) have emerged as promising biomarkers for early cancer detection. This research aimed to assess the diagnostic capacity of anti-BIRC5 autoantibody in detecting AFP-negative hepatocellular carcinoma (ANHCC). Methods This research was carried out in three stages (discovery phase, validation phase, and evaluation phase) and included a total of 744 participants. Firstly, the anti-BIRC5 autoantibody was discovered using protein microarray, exhibiting a higher positive rate in ANHCC samples (ANHCCs) compared to normal control samples (NCs). Secondly, the anti-BIRC5 autoantibody was validated through enzyme-linked immunosorbent assay (ELISA) in 85 ANHCCs and 85 NCs from two clinical centers (Zhengzhou and Nanchang). Lastly, the diagnostic usefulness of the anti-BIRC5 autoantibody for hepatocellular carcinoma (HCC) was evaluated by ELISA in a cohort consisting of an additional 149 AFP-positive hepatocellular carcinoma samples (APHCCs), 95 ANHCCs and 244 NCs. The association of elevated autoantibody to high expression of BIRC5 in HCC was further explored by the database from prognosis, immune infiltration, DNA methylation, and gene mutation level. Results In the validation phase, the area under the ROC curve (AUC) of anti-BIRC5 autoantibody to distinguish ANHCCs from NCs in Zhengzhou and Nanchang centers was 0.733 and 0.745, respectively. In the evaluation phase, the AUCs of anti-BIRC5 autoantibody for identifying ANHCCs and HCCs from NCs were 0.738 and 0.726, respectively. Furthermore, when combined with AFP, the AUC for identifying HCCs from NCs increased to 0.914 with a sensitivity of 77.5% and specificity of 91.8%. High expression of BIRC5 gene is not only correlated with poor prognosis of HCCs, but also significantly associated with infiltration of immune cells, DNA methylation, and gene mutation. Conclusion The findings suggest that the anti-BIRC5 autoantibody could serve as a potential biomarker for ANHCC, in addition to its supplementary role alongside AFP in the diagnosis of HCC. Next, we can carry out specific verification and explore the function of anti-BIRC5 autoantibody in the occurrence and development of HCC.

A close relationship between fatty acid metabolism and cancer development is well-established. The hydroxyacyl-coenzyme a dehydrogenase (HADH), a key enzyme in fatty acid beta-oxidation, has recently been identified as an anti-oncogenic factor in various cancers and an oncogenic factor in conditions like acute myeloid leukemia. In cancer cells, HADH not only directly catalyzes fatty acid beta-oxidation but also indirectly influences multiple signaling pathways such as PPAR, TNF-α, JAK-STAT3, PI3K/Akt, IFN-γ, MAPK, and non-canonical Wnt signaling pathways, affecting cancer cell proliferation and migration. HADH shows promise as a potential tumor biomarker for diagnosis, treatment, and prognosis in different cancer types, holding significant clinical value.

Abstract Background CA15-3 is often elevated in breast cancer recurrence and rarely in ductal carcinoma in situ (DCIS). We report a case of DCIS with elevated CA15-3 levels, which was diagnosed after over 2 years of follow-up. Case presentation A 74-year-old woman presented with a left-sided breast mass and pain. Redness, swelling, and induration were observed in the left breast. Ultrasonography revealed a non-mass lesion in the left 3 o'clock position, skin thickening, and axillary lymphadenopathy. Serum CA15-3 levels were markedly high at 640 U/mL, suggesting inflammatory breast cancer. However, biopsies showed no malignancy. We diagnosed chronic mastitis with elevated CA15-3 levels and followed up with magnetic resonance imaging and a biopsy, as needed. Finally, DCIS was diagnosed 27 months after the first visit. She underwent a left mastectomy and a sentinel lymph node biopsy; DCIS had spread 6.5 cm and was immunohistochemically positive for CA15-3. No metastasis was found in the lymph nodes, but incidental Hodgkin lymphoma was observed. Postoperative normalization of CA15-3 levels indicated that she had DCIS with elevated CA15-3 levels. The patient underwent chemotherapy for Hodgkin lymphoma postoperatively, and there was no evidence of recurrence 1 year after surgery. Conclusion High CA15-3 levels can also be observed in DCIS, indicating that CA15-3 should not be used solely in breast cancer staging.

Objective To explore the effect of paclitaxel with carboplatin combined chemotherapy on hemocyte related indexes,vascular endothelial growth factor (VEGF) and tumor markers in ovarian cancer (OC) patients. Methods OC patients combined chemotherapy (CC) group and ovarian benign tumor control group with 50 cases in each. The pathological changes in the ovarian cells were observed by HE staining and the expression of VEGF was observed by immunohistochemical staining (IHC).Blood cell was counted by flow cytometry (FC). Serum carbohydrate antigen 125 (CA125) and human epididymal protein 4 (HE4) were measured by electrochemical luminescence (ECL). Results Compared with control group, the ovarian tissue structure was disordered and the cell atypia was obvious in OC.VEGF expression was significantly enhanced. Platelet count (PLT), CA125 and HE4 were significantly increased (P＜0.01). However,necrotic cells were observed in ovarian tissue of CC group.VEGF expression was inhibited.PLT count and the level of CA125 and HE4 were significantly lower than those of control group after chemotherapy(P＜0.01). Conclusions Combined chemotherapy may regulate the level of VEGF, CA125 and HE4 in OC patients.

Background: Nectin-4 is a novel biomarker overexpressed in various types of cancer, including breast cancer, in which it has been associated with poor prognosis. Current literature suggests that nectin-4 has a role in cancer progression and may have prognostic and therapeutic implications. The present study aims to produce nectin-4-specific single-chain variable fragment (scFv) antibodies and evaluate their applications in breast cancer cell lines and clinical specimens. Methods: We generated recombinant nectin-4 ectodomain fragments as immunogens to immunize chickens and the chickens' immunoglobulin genes were amplified for construction of anti-nectin-4 scFv libraries using phage display. The binding capacities of the selected clones were evaluated with the recombinant nectin-4 fragments, breast cancer cell lines, and paraffin-embedded tissue sections using various laboratory approaches. The binding affinity and in silico docking profile were also characterized. Results: We have selected two clones (S21 and L4) from the libraries with superior binding capacity. S21 yielded higher signals when used as the primry antibody for western blot analysis and flow cytometry, whereas clone L4 generated cleaner and stronger signals in immunofluorescence and immunohistochemistry staining. In addition, both scFvs could diminish attachment-free cell aggregation of nectin-4-positive breast cancer cells. As results from ELISA indicated that L4 bound more efficiently to fixed nectin-4 ectodomain, molecular docking analysis was further performed and demonstrated that L4 possesses multiple polar contacts with nectin-4 and diversity in interacting residues. Conclusion: Overall, the nectin-4-specific scFvs could recognize nectin-4 expressed by breast cancer cells and have the merit of being further explored for potential diagnostic and therapeutic applications. [ABSTRACT FROM AUTHOR]

Objective To explore the effect of EMT pathway on the prognosis of the patients with melanoma and the correlation between common tumor markers and EMT pathway to provide the new ideas for clinical identification and follow-up of melanoma patients with high risk of metastasis. Methods The transcriptional and clinical data of 461 melanoma patients were obtained from the TCGA database. The expression of each sample was analyzed by GSVA package with non-parametric unsupervised analysis, and the expression score of EMT pathway was obtained and divided into the low and high groups. The survival package was used for conducting the survival analysis. Then the mRNA and EMT pathway expression levels of tumor markers conducted the Spearman correlation analysis, moreover the subgroup analysis was performed according to age, sex and tumor stage. The protein expression levels of tumor markers in melanoma patients were further downloaded from the TCGA database, and the correlation analysis was also conducted to explore the correlation between the common tumor markers and EMT pathways from two perspectives of mRNA and protein expression levels. Finally, the above tumor markers, EMT pathway expression levels and clinical features were included in a multi-factor analysis to determine their impact on melanoma prognosis. Results The high expression of EMT pathway predicted the poor prognosis of melanoma patients. The mRNA expression levels of melanoma tumor markers PMEL, MLANA, TYR, and MITF were negatively correlated with the EMT pathway (P<0.05), while the mRNA expression level of MKI67 was positively correlated with the EMT pathway (P<0.05). The results of subgroup analysis of the correlation between the tumor markers and EMT pathway were basically consistent with those obtained in the total sample. High expression of tumor marker PMEL and low expression of EMT-related pathway predicted a good prognosis, while low expression of MLANA and MKI67 predicted a good prognosis when EMT-related pathway was low expression (P<0.05). The protein expression levels of PMEL, MLANA and MITF were negatively correlated with the expression of EMT pathway (P<0.05). PMEL, age and tumor stage might be the independent risk factors for melanoma prognosis. Conclusion The lower expressions of PMEL, MLANA and MITF common markers of melanoma may be related to the high expression of EMT pathway. When the EMT-related pathways are low, high expression of PMEL and MLANA and low expression of MKI67 predict a good prognosis, which should be paid a certain degree of attention to during follow-up. [ABSTRACT FROM AUTHOR]