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Levels of the serum tumor markers (STMs) α-fetoprotein, human chorionic gonadotropin, and lactate dehydrogenase are used in staging classification for metastatic germ-cell cancers and support decisions on the intensity of first-line treatment for patients with nonseminoma. Use of preorchiectomy instead of prechemotherapy STM levels can lead to inadequate classification. We identified 744 men with metastatic gonadal nonseminoma in the International Germ-Cell Cancer Collaborative Group (IGCCCG) Update Consortium database who had preorchiectomy and prechemotherapy STM levels available. Of these, 22% would have had inadequate IGCCCG prognostic group classification if preorchiectomy levels had been used, which would have resulted in overtreatment of 16% and undertreatment of 6% of men. These findings suggest that use of preorchiectomy instead of prechemotherapy STM results may lead to incorrect IGCCCG classification, which could compromise treatment success or expose patients to unnecessary toxicity. Patient summary: For men with testicular cancer, levels of tumor markers in their blood are used when making decisions on chemotherapy intensity. Use of test results for samples taken before removal of the cancer-bearing testicle instead of immediately before chemotherapy can lead to inadequate treatment recommendations.

Sphingolipid metabolism affects prognosis and resistance to immunotherapy in patients with cancer and is an emerging target in cancer therapy with promising diagnostic and prognostic value. Long noncoding ribonucleic acids (lncRNAs) broadly regulate tumour-associated metabolic reprogramming. However, the potential of sphingolipid metabolism-related lncRNAs in pancreatic adenocarcinoma (PAAD) is poorly understood. In this study, coexpression algorithms were employed to identify sphingolipid metabolism-related lncRNAs. The least absolute shrinkage and selection operator (LASSO) algorithm was used to develop a sphingolipid metabolism-related lncRNA signature (SMLs). The prognostic predictive stability of the SMLs was validated using Kaplan–Meier. Univariate and multivariate Cox, receiver operating characteristic (ROC) and clinical stratification analyses were used to comprehensively assess the SMLs. Gene set variation analysis (GSVE), gene ontology (GO) and tumor mutation burden (TMB) analysis explored the potential mechanisms. Additionally, single sample gene set enrichment analysis (ssGSEA), ESTIMATE, immune checkpoints and drug sensitivity analysis were used to investigate the potential predictive function of the SMLs. Finally, an SMLs-based consensus clustering algorithm was utilized to differentiate patients and determine the suitable population for immunotherapy. The results showed that the SMLs consists of seven sphingolipid metabolism-related lncRNAs, which can well determine the clinical outcome of individuals with PAAD, with high stability and general applicability. In addition, the SMLs-based consensus clustering algorithm divided the TCGA-PAAD cohort into two clusters, with Cluster 1 showing better survival than Cluster 2. Additionally, Cluster 1 had a higher level of immune cell infiltration than Cluster 2, which combined with the higher levels of immune checkpoints in Cluster 1 suggests that Cluster 1 is more consistent with an immune ‘hot tumor’ profile and may respond better to immune checkpoint inhibitors (ICIs). This study offers new insights regarding the potential role of sphingolipid metabolism-related lncRNAs as biomarkers in PAAD. The constructed SMLs and the SMLs-based clustering are valuable tools for predicting clinical outcomes in PAAD and provide a basis for clinical selection of individualized treatments.

WNT inhibitory factor 1 (WIF1) is known to function as a tumor suppressor gene; it inhibits oncogene activation by preventing WNT signaling. This study investigated the epigenetic regulation of WIF1 gene in bladder cancer. We observed a positive relationship between WIF1 mRNA expression and survival probability of bladder cancer patients. The WIF1 gene expression could be enhanced by DNA demethylation drug 5-aza-2′-deoxycytidine (5-aza-dC) and histone deacetylase inhibitor trichostatin A (TSA), suggesting that epigenetic modifications could regulate WIF1 gene expression. Overexpression of WIF1 inhibited cell proliferation and migration in 5637 cells, confirming the tumor suppressor role of WIF1. 5-Aza-dC dose dependently increased WIF1 gene expression while reducing DNA methylation level, suggesting that reversing WIF1 DNA methylation could activate its gene expression. We collected the cancer tissues and urine pellets of bladder cancer patients and only urine pellets from non-bladder cancer volunteers for DNA methylation analysis, but the methylation level of WIF1 gene −184 to +29 did not differ between patients and controls. We also analyzed glutathione S-transferase Mu 5 (GSTM5) gene methylation level because GSTM5 DNA hypermethylation was suggested to be a tumor biomarker in our previous study. It confirmed a higher GSTM5 DNA methylation in bladder cancer patients than in controls. In summary, this study suggests that the 5-aza-dC activated WIF1 gene which showed an anti-cancer effect, while WIF1 promoter −184 to +29 did not provide a suitable methylation assay region in clinical samples. In contrast, GSTM5 promoter −258 to −89 is a useful region for DNA methylation assay because it shows a higher methylation level in bladder cancer patients.

Sensitive detection of tumor biomarkers is of great significance for early cancer diagnosis, treatment evaluation, and recurrence monitoring. Development of convenient electrochemiluminescence (ECL) immunosensor using dissolved oxygen (O 2 ) as an endogenous co-reactant of luminol combined with efficient nanocatalysts to boost ECL signal in neutral media is highly desirable. Herein, sensitive detection of tumor biomarker using ECL of luminal-O 2 enhanced by confinement of nitrogen-doped graphene quantum dots (N-GQDs) and platinum nanoparticles (PtNPs) on nanochannel array was demonstrated. A high-density nanochannel array-modified electrode was achieved by rapidly growing an amino-functionalized. Vertically-ordered mesoporous silica film (NH 2 -VMSF) on the inexpensive and readily available indium tin oxide (ITO) electrode. Through simple electrodeposition, N-GQDs were confined and PtNPs were in-situ synthesized in nanochannels of NH 2 -VMSF. These confined nanocomposites catalyzed the electroreduction of O 2  at negative potentials to generate a large amount of reactive oxygen species (ROS) and facilitated luminol oxidation, enhancing the ECL signal of luminol by 25 times. Two immunosensors were fabricated after covalent immobilization of the recognition antibody of carbohydrate antigen 199 (CA199) or carbohydrate antigen 125 (CA125) on the outer surface of the NH 2 -VMSF and blocking of non-specific sites. When tumor biomarkers bind to the corresponding antibodies on the recognition interface, the formed immunocomplex hindered the diffusion of luminol to the underlying electrode, resulting in a decrease in the ECL signal and sensitive detection of tumor biomarker. The constructed CA199 immunosensor exhibited a linear detection range for CA199 from 0.5 mU mL -1  to 50 U mL -1 , with a detection limit (DL) of 0.03 mU mL -1 . For CA125 detection, linear detection ranged from 0.5 mU mL -1  to 500 U mL -1 , with a DL of 0.005 mU mL -1 . The fabricated immunosensors demonstrated good selectivity and high reproducibility. This study provides great potential for the development of efficient luminol ECL systems in neutral media and expands the biological application in sensitive detection of tumor biomarker., 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.)

The detection of pre-invasive tumors prior to the appearance of advanced clinical symptoms will enhance the effect of medical intervention at the earliest stage and reduce premature cancer deaths. Tumor biomarkers detection represents a powerful alternative to taking invasive biopsies; hence, biosensing technology is emphasized. Cancer diagnostics have evolved from the macroscopic detection of malignant tumors to the facile assessment of tumor biomarkers using miniaturized detection devices, such as immunosensors. Innovative immunosensors have become the most eminent candidate for analyzing oncomarkers to meet the requirements of medical diagnostics. Hence the development of highly selective immunosensors for the sensitive detection of oncomarker paves new directions for personal and medical supervision. Graphene and its derivatives are emerging carbon materials employed in developing sensors, in view of their exceptional physicochemical properties that amplify the device's sensitivity. Therefore, this review was designed to present a comprehensive interpretation of the recently developed graphene-based electrochemical immunosensors for detecting broad-spectrum oncomarker carcinoembryonic antigen (CEA). The article highlights the recent advances in signal amplification strategies accomplished utilizing graphene and its nanomaterials (2017 to mid-2022). Different electroanalytical techniques employed for CEA sensing have been discussed, and the sensor's performances are substantiated. The readers are also provided with significant statistical information on the reported immunosensors and their performance comparison: a technique used, working range, detection limit, real sample recoveries, reproducibility, and stability. Finally, the review concludes with the associated challenges and outlines the approach required to realize their successful translation into clinical settings.

Objective: The objective of this study was to assess the correlation between the expression of HSP70-2 and the development of oral potentially malignant disorders (OPMD) and oral squamous cell carcinoma (OSCC). Furthermore, the study evaluates the potential function of HSP70-2 in the pathogenesis of malignant diseases of the oral cavity., Methods: Using immunohistochemistry, RT-qPCR, Western blot, indirect immunofluorescence, and flow cytometry, the expression of HSP70-2 mRNA and protein in OPMD and OSCC tissues and cells was investigated. Using liposomal vector transient transfection to specifically knock down HSP70-2 gene expression in pertinent cell lines in vitro, the role of HSP70-2 in the development of oral malignant disorders was further investigated., Results: Studies on OPMD and OSCC tissues and cell lines revealed that HSP70-2 mRNA and protein were substantially expressed. Furthermore, it was discovered that the expression levels corresponded with the degree of disease development. Downregulating the HSP70-2 gene specifically reduces the proliferation, viability, colony-forming ability, migration, and invasion of OPMD and OSCC cells. Furthermore, it will cause apoptosis and control cell cycle arrest., Conclusion: HSP70-2 exhibited a significantly differential expression in both NM, OPMD, and OSCC tissues and cells. Furthermore, HSP70-2 plays a function in the development of oral malignant illnesses., Clinical Relevance: HSP70-2 is a promising biomarker for predicting the malignant transformation of Oral leukoplakia (OLK) and early diagnosis of OSCC. It is highly anticipated that HSP70-2 will be a potential target for the early intervention and blockage of OLK malignant transformation, given its established role in the development of oral malignant disorders. With regard to the treatment of OSCC, the same provides a referable target for siRNA-based therapeutic modalities., 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 Inc. All rights reserved.)

Dysregulated surface glycoproteins play an important role in tumor cell proliferation and progression. Abnormal glycosylation of these glycoproteins may activate tumor signal transduction and lead to tumor development. The tumor microenvironment alters its molecular composition, some of which regulate protein glycosylation biosynthesis. The glycosylation of saliva proteins in lung cancer patients is different from healthy controls, in which the glycans of cancer patients are highly sialylated and hyperfucosylated. Most studies have shown that O-glycans from cancer are truncated O-glycans, while N-glycans contain fucoses and sialic acids. Because glycosylation analysis is challenging, there are few reports on how glycosylation of saliva proteins is related to the occurrence or progression of lung cancer. In this review, we discussed glycoenzymes involved in protein glycosylation, their changes in tumor microenvironment, potential tumor biomarkers present in body fluids, and abnormal glycosylation of saliva or lung glycoproteins. We further explored the effect of glycosylation changes on tumor signal transduction, and emphasized the role of receptor tyrosine kinases in tumorigenesis and metastasis.

Background: The incorporation of circulating tumor DNA (ctDNA) into the management of operable breast cancer (BC) has been hampered by the heterogeneous results from different studies. We aimed to assess the prognostic value of ctDNA in patients with operable (non metastatic) BC., Materials and Methods: A systematic search of databases (PubMed/Medline, Embase, and CENTRAL) and conference proceedings was conducted to identify studies reporting the association of ctDNA detection with disease-free survival (DFS) and overall survival (OS) in patients with stage I-III BC. Log-hazard ratios (HRs) were pooled at each timepoint of ctDNA assessment (baseline, after neoadjuvant therapy, and follow-up). ctDNA assays were classified as primary tumor-informed and non tumor-informed., Results: Of the 3174 records identified, 57 studies including 5779 patients were eligible. In univariate analyses, ctDNA detection was associated with worse DFS at baseline [HR 2.98, 95% confidence interval (CI) 1.92-4.63], after neoadjuvant therapy (HR 7.69, 95% CI 4.83-12.24), and during follow-up (HR 14.04, 95% CI 7.55-26.11). Similarly, ctDNA detection at all timepoints was associated with worse OS (at baseline: HR 2.76, 95% CI 1.60-4.77; after neoadjuvant therapy: HR 2.72, 95% CI 1.44-5.14; and during follow-up: HR 9.19, 95% CI 3.26-25.90). Similar DFS and OS results were observed in multivariate analyses. Pooled HRs were numerically higher when ctDNA was detected at the end of neoadjuvant therapy or during follow-up and for primary tumor-informed assays. ctDNA detection sensitivity and specificity for BC recurrence ranged from 0.31 to 1.0 and 0.7 to 1.0, respectively. The mean lead time from ctDNA detection to overt recurrence was 10.81 months (range 0-58.9 months)., Conclusions: ctDNA detection was associated with worse DFS and OS in patients with operable BC, particularly when detected after treatment and using primary tumor-informed assays. ctDNA detection has a high specificity for anticipating BC relapse., Competing Interests: Disclosure GNM reports meeting/travel grants from AstraZeneca. EA reports consultancy fees/honoraria from Eli Lilly, Sandoz, and AstraZeneca; research grant to the institution from Gilead; meeting/travel grants from Novartis, Roche, Eli Lilly, Genetic, Istituto Gentili, Daiichi Sankyo, and AstraZeneca (all outside the submitted work). DMB reports full time employment at European Society for Medical Oncology since September 1, 2023; speaker’s engagement from Daiichi Sankyo/AstraZeneca; participation as medical research fellow in research studies with institutionally funded by Eli Lilly, Novartis, and F. Hoffmann-La Roche Ltd to Institut Jules Bordet; non-financial interest as member of the board of directors for Associaҫão de Investigaҫão e Ciudados de Suporte em Oncologia; non-remunerated prior leadership role as Portuguese Young Oncologists Committee Chair from Sociedade Portuguesa de Oncologia (all outside the submitted work). ALC reports leadership role at Eisai, Celgene, Lilly, Pfizer, Roche, Novartis, and MSD; intellectual property for MEDSIR; a consulting role for Lilly, Roche, Pfizer, Novartis, Pierre-Fabre, Exact Sciences, Seagen, and GSK; to be part of the speaker bureau for Lilly, AstraZeneca, and MSD; to receive research funding from Pfizer, Roche, Foundation Medicine, Exact Sciences, Pierre-Fabre, and Agendia; and travel compensation from Roche, Lilly, Novartis, Pfizer, and AstraZeneca. JC reports consulting/advisor role for Roche, Celgene, Cellestia, AstraZeneca, Seattle Genetics, Daiichi Sankyo, Erytech, Athenex, Polyphor, Lilly, Merck Sharp & Dohme, GSK, Leuko, Bioasis, Clovis Oncology, Boehringer Ingelheim, Ellipses, HiberCell, BioInvent, GEMoaB, Gilead, Menarini, Zymeworks, Reveal Genomics, Expres2ion Biotechnologies, Jazz Pharmaceuticals, and AbbVie; honoraria from Roche, Novartis, Celgene, Eisai, Pfizer, Samsung Bioepis, Lilly, Merck Sharp & Dohme, Daiichi Sankyo, AstraZeneca; research funding to the institution from Roche, Ariad pharmaceuticals, AstraZeneca, Baxalta GMBH/Servier Affaires, Bayer healthcare, Eisai, F. Hoffmann-La Roche, Guardant Health, Merck Sharp & Dohme, Pfizer, PIQUR Therapeutics, IQVIA, and Queen Mary University of London; stocks from MAJ3 Capital and Leuko (relative); travel, accommodation, and other expenses covered by Roche, Novartis, Eisai, Pfizer, Daiichi Sankyo, AstraZeneca, Gilead, and Merck Sharp & Dohme; patents ‘Pharmaceutical Combinations of A Pi3k Inhibitor And A Microtubule Destabilizing Agent’—Javier Cortés Castán, Alejandro Piris Giménez, Violeta Serra Elizalde, WO 2014/199294 A (issued) and ‘Her2 as a predictor of response to dual HER2 blockade in the absence of cytotoxic therapy’—Aleix Prat, Antonio Llombart, Javier Cortés, US 2019/ 0338368 A1 (licensed). MI reports honoraria from Novartis and Seattle Genetics; research support to the institution from Natera Inc, Inivata, Roche, and Pfizer; and travel grants from Roche and Gilead. GP reports being part of the advisory board/speaker bureau for Roche, Bayer, AstraZeneca, Novartis, Illumina, and ADS Biotech; and grants from Candriam and Thermo Fisher. EA reports honoraria and/or being part of the advisory board for Roche/GNE, Novartis, Seagen, Zodiac, Libbs, Pierre Fabre, Lilly, and Astra-Zeneca; travel grants from Roche/GNE and AstraZeneca; research grant to the institution from Roche/GNE, Astra-Zeneca, and GSK/Novartis. SDC reports being on the speaker’s bureau for AstraZeneca; and on the advisory board for Pierre-Fabre, IQVIA, and MEDSIR. All other authors have declared no conflicts of interest., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Circulating Hsp70 levels were determined in feline and porcine cohorts using two different ELISA systems. These comparative animal models of larger organisms often reflect diseases, and especially malignant tumors, better than conventional rodent models. It is therefore essential to investigate the biology and utility of tumor biomarkers in animals such as cats and pigs. In this study, levels of free Hsp70 in the blood of cats with spontaneously occurring tumors were detected using a commercial Hsp70 ELISA (R&D Systems). Sub-analysis of different tumor groups revealed that animals with tumors of epithelial origin presented with significantly elevated circulating Hsp70 concentrations. In addition to free Hsp70 levels measured with the R&D Systems Hsp70 ELISA, levels of exosomal Hsp70 were determined using the compHsp70 ELISA in pigs. Both ELISA systems detected significantly elevated Hsp70 levels (R&D Systems: median 24.9 ng/mL; compHsp70: median 44.2 ng/mL) in the blood of a cohort of APC 1311/+ pigs diagnosed with high-grade adenoma polyps, and the R&D Systems Hsp70 ELISA detected also elevated Hsp70 levels in animals with low-grade polyps. In contrast, in flTP53 R167H pigs, suffering from malignant osteosarcoma, the compHsp70 ELISA (median 674.32 ng/mL), but not the R&D Systems Hsp70 ELISA (median 4.78 ng/mL), determined significantly elevated Hsp70 concentrations, indicating that in tumor-bearing animals, the dominant form of Hsp70 is of exosomal origin. Our data suggest that both ELISA systems are suitable for detecting free circulating Hsp70 levels in pigs with high-grade adenoma, but only the compHsp70 ELISA can measure elevated, tumor-derived exosomal Hsp70 levels in tumor-bearing animals., (© 2022. The Author(s).)

Introduction: Brigatinib is a potent next-generation ALK tyrosine kinase inhibitor approved for treatment-naive and crizotinib-refractory advanced ALK-positive (ALK+) NSCLC. We evaluated brigatinib after other next-generation ALK tyrosine kinase inhibitors., Methods: In this single-arm, phase 2, ALK in Lung Cancer Trial of brigAtinib-2 (NCT03535740), patients with advanced ALK+ NSCLC whose disease progressed on alectinib or ceritinib received brigatinib 180 mg once daily (after 7-d 90-mg lead-in). Primary end point was independent review committee (IRC)-assessed overall response rate (ORR). Circulating tumor DNA (ctDNA) was analyzed., Results: Among 103 patients (data cutoff: September 30, 2020; median follow-up [range]: 10.8 [0.5-17.7] mo), confirmed IRC-ORR was 26.2% (95% confidence interval [CI]: 18.0-35.8), median duration of response, 6.3 months (95% CI: 5.6-not reached), and median progression-free survival (mPFS), 3.8 months (95% CI: 3.5-5.8). mPFS was 1.9 months (95% CI: 1.8-3.7) in patients with ctDNA-detectable baseline ALK fusion (n = 64). Among 86 patients who progressed on alectinib, IRC-ORR was 29.1% (95% CI: 19.8-39.9); mPFS was 3.8 months (95% CI: 1.9-5.4). Resistance mutations were present in 33.3% (26 of 78) of baseline ctDNA; 54% (14 of 26) of mutations were G1202R; 52% (33 of 64) of patients with detectable ALK fusion had EML4-ALK variant 3. Most common all-grade treatment-related adverse events were increased creatine phosphokinase (32%) and diarrhea (27%). The mean dose intensity of brigatinib (180 mg once daily) was 85.9%., Conclusions: In ALK in Lung Cancer Trial of brigAtinib-2, brigatinib was found to have a limited activity in patients with ALK+ NSCLC post-ceritinib or post-alectinib therapy. mPFS was longer with brigatinib in patients without baseline detectable plasma ALK fusion., (Copyright © 2022 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

Glycosylation is a critical post-translational modification (PTM) that affects the function of proteins and regulates cell signaling, thereby regulating various biological processes. Protein oxygen-N-acetylglucosamine (O-GlcNAc) glycosylation modifications are glycochemical modifications that occur within cells in the signal transduction and are frequently found in the cytoplasm and nucleus. Due to the rapid and reversible addition and removal, O-GlcNAc modifications are able to reversibly compete with certain phosphorylation modifications, immediately regulate the activity of proteins, and participate in kinds of cellular metabolic and signal transduction pathways, playing a pivotal role in the regulation of tumors, diabetes, and other diseases. This article provided a brief overview of O-GlcNAc glycosylation modification, introduced its role in altering the progression and immune response regulation of gastrointestinal tumors, and discussed its potential use as a marker of tumor neogenesis., Competing Interests: Conflict of interest No authors report any conflict of interest., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Biomarkers play an important role in disease diagnosis and prognosis, which demand reliable, sensitive, rapid, and economic detection platform to conduct simultaneous multiple-biomarkers analysis in serum or body liquid. Here, we developed a universal biosensing platform through integrating the advantages of unique nanostructure and biochemistry properties of graphene oxide quantum dots and high throughput and low cost of microfluidic chip for reliable and simultaneous detection of multiple cancer antigen and antibody biomarkers. The performance of the proposed biosensing platform is validated through the representative cancer biomarkers including carcino-embryonic antigen (CEA), carbohydrate antigen 125 (CA125), α-fetoprotein (AFP), carbohydrate antigen 199 (CA199) and carbohydrate antigen 153 (CA153). It has a large linear quantification detection regime of 5-6 orders of magnitude and an ultralow detection limit of 1 pg/mL or 0.01 U/mL. Moreover, the proposed biosensing chip is capable of conducting 5-20 kinds of biomarkers from at least 60 persons simultaneously in 40 min with only 2 μL serum of each patient, which essentially reduces the detection cost and time to at least 1/60 of current popular methods. Clinical breast cancer and healthy samples detection results indicated its promising perspective in practical applications including cancer early diagnosis, prognosis, and disease pathogenesis study., 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 © 2021 Elsevier B.V. All rights reserved.)

Late diagnosis of pancreatic ductal adenocarcinoma (PDA) is one of the reasons of its low 5-year survival rate and it is due to its unspecific symptoms during the first stages of the disease and the lack of reliable serological markers. Since PDA shows an altered glycan expression, here we have focused on finding novel potential biomarkers, namely glycoproteins that express the tumor associated carbohydrate structure sialyl-Lewis x (sLe x ), which is described in PDA. Through a glycoproteomic approach, we have analyzed target proteins containing sLe x from PDA tissues by 2DE and immunodetection techniques, and have identified by mass spectrometry the protein MFAP4 as a carrier of sLe x in PDA. MFAP4 showed a higher expression in PDA tissues compared with pancreatic control tissues. In addition, the colocalization of sLe x over MFAP4 was found only in PDA and not in control pancreatic tissues. The analysis of MFAP4 expression in PDA cell lines and their secretome, in combination with immunohistochemistry of pancreatic tissues, revealed that MFAP4 was not produced by PDA cells, but it was found in the pancreatic extracellular matrix. The specificity of MFAP4 glycoform containing sLe x in PDA tissues shows its relevance as a potential PDA biomarker. SIGNIFICANCE: Despite advances in the field of cancer research, pancreatic ductal adenocarcinoma (PDA) lacks of a specific and sensitive biomarker for its early detection, when curative resection is still possible before metastases arise. Thus, efforts to discover new PDA biomarkers represent the first line in the fight against the increase of its incidence reported in recent years. Glycan alterations on glycoconjugates, such as glycoproteins have emerged as a rich source for the identification of novel cancer markers. In the present work, we aimed to shed light on novel biomarkers based on altered glycosylation in PDA, in particular those glycoproteins of PDA tissues carrying the tumor carbohydrate antigen sialyl-Lewis x (sLe x ). Through a glycoproteomic approach, we have shown that the glycoprotein MFAP4 carries sLe x in PDA tissues and not in control pancreatic tissues. MFAP4 is found in the extracellular matrix in PDA and although its role in cancer progression is unclear, its sLe x glycoform could be a potential biomarker in pancreatic ductal adenocarcinoma., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Pancreatic cancer (PaCa) is considered an aggressive but still asymptomatic malignancy. Due to the lack of effective diagnostic markers, PaCa is often diagnosed during late metastatic stages. Besides surgical resection, no other treatment appears to be effective during earlier stages of the disease. Exosomes are related to a class of nanovesicles coated by a bilayer lipid membrane and enriched in protein, nucleic acid, and lipid contents. They are widely present in human body fluids, including blood, saliva, and pancreatic duct fluid, with functions in signal transduction and material transport. A large number of studies have suggested for a crucial role for exosomes in PaCa, which may be utilized to improve its future diagnosis and treatment, but the underlying molecular mechanisms as well as their potential clinical applications are largely unknown. By collecting and analyzing the most up-to-date literature, here we summarize the current progress of the clinical applications related to exosomes in PaCa. Therefore, we presently provide some rationale for the potential value of exosomes in PaCa, thereby promoting putative applications in targeted PaCa treatment., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Carcinoembryonic antigen (CEA) is a well-known cancer biomarker for the detection of several malignancies. The development of ultrasensitive CEA diagnostic tools is crucial for early detection and progression observation of tumors. Herein, a dual signal amplified sandwich-type electrochemical immunoassay was developed based on dual-labeled mesoporous silica nanospheres as a signal amplifier, combined with NiO@Au decorated graphene as a conductive layer for ultrasensitive and rapid determination of CEA. The dual-labeled mesoporous silica (DLMS) nanosphere, which was synthesized by entrapping Au nanorod (Au NR) and horseradish peroxidase (HRP) in the channels of amine-functionalized SBA-15 followed by subordinate antibody (Ab 2 ) conjugation which was denoted as Au NR@SBA-15/Ab 2 -HRP. The dual signal amplification from Au NR@SBA-15 and HRP enhanced the sensitivity of the proposed immunoassay. Consequently, the developed DLMS based immunosensor displayed ultra-low limits of detection of 5.25 fg/mL and a wide range of linearity (0.1-5 pg/mL), which was extended for CEA determination in real-time samples with improved recoveries of >98%. Therefore, this dual amplification prototype would cater to the clinical requirements for the ultrasensitive detection of CEA biomarkers., 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 © 2020. Published by Elsevier B.V.)

The concentration of circulating heat shock protein 70 (Hsp70) was measured in liquid biopsies of canine tumor patients as a potential biomarker. Compared with rodent tumor models, spontaneously occurring tumors in pet dogs reflect the clinical situation of human patients better, as dogs cohabitate with their owners in the same environment, reach a much older age than rodents, can provide blood samples much more frequently, and receive up-to-date medical care and, similar to humans, their tumors show a high genetic heterogeneity. Due to the species-specific sequence homology of human and canine Hsp70, two human enzyme-linked immunosorbent assay (ELISA) systems (R&D and lipHsp70) were used to measure canine Hsp70 concentrations in serum and plasma. In general, higher Hsp70 concentrations were found in serum compared with plasma samples of dogs, and the lipHsp70 ELISA detected higher peak concentrations of Hsp70 in a broader range than the R&D ELISA. Compared with a tumor-free control group, serum Hsp70 concentrations were higher in tumor-bearing dogs, irrespective of breed, age, body weight, and gender. A sub-classification of the different tumors according to their cytological characteristics revealed significantly elevated Hsp70 serum concentrations in dogs with round cell tumors (p < 0.01), a heterogeneous group of malignancies with hematopoietic origin such as mast cells, plasma cells, lymphocytes, histiocytes, and melanomas. Future studies with larger patient cohorts and well-defined tumor sizes are necessary to elucidate the role of serum Hsp70 as a biomarker for tumor detection and monitoring of outcome in pet animals.

Background: Serum-based tumor biomarkers are used to monitor cancer treatment, while clear guidance on the clinical usage is often lacking. We describe a graphical presentation to support diagnostic accuracy studies and clinical interpretation of longitudinal biomarker data., Methods: A biomarker response characteristic (BReC) plot was designed. To allow demonstration of the BReC plot application, software was developed that supported 1) dynamic generation of BReC plots, and 2) diagnostic accuracy studies of biomarker response-based medical tests. The BReC plot application was demonstrated using serial carcinoembryonic antigen (CEA) and Cyfra 21.1 results from 216 patients with metastasized non-small cell lung cancer, treated with Nivolumab in routine clinical practice., Results: The developed software supported the generation of BReC plots and diagnostic validation of biomarker response-based medical tests by generating the sensitivity, specificity and predictive values. Obtained BReC plots showed a clear relationship between clinical outcome and CEA and Cyfra 21.1 responses. Furthermore, using BReC plots, CEA and Cyfra 21.1 based medical tests were designed with a sensitivity for detection of treatment failure of 0.34 and 0.35 and a specificity of 0.96., Conclusions: The BReC plot appears to support diagnostic validation studies and the interpretation of longitudinal biomarkers though further validation is warranted., (Copyright © 2018 Elsevier B.V. All rights reserved.)

In this work, a new conductive hydrogel was prepared by a simple cross-linking coordination method using 1,3,5-benzenetricarboxylic acid as the ligand and Fe 3+ as the metal ion. The hydrogel film was formed on a glassy carbon electrode (GCE) by a drop coating method, which can dramatically facilitate the transport of electrons. A sensitive label-free electrochemical immunosensor was fabricated following electrodeposition of gold nanoparticles (AuNPs) on a hydrogel film and immobilization of an antibody. Neuron-specific enolase (NSE), a lung cancer biomarker, was used as the model analyte to be detected. The proposed immunosensor exhibited a wide linear detection range of 1pgmL -1 to 200ngmL -1 and a limit of detection of 0.26pgmL -1 (the ratio of signal to noise (S/N)=3). Moreover, the detection of NSE in human serum samples showed satisfactory accuracy compared with the data determined by enzyme-linked immunosorbent assay (ELISA), indicating good analytical performance of the immunoassay., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background: The B7 family member B7-H3 (CD276) is involved in tumor immunity including Non-small-cell lung cancer (NSCLC). We have previously demonstrated an elevated circulating level of the soluble form of B7-H3 (sB7-H3) in NSCLC patients. However, the expression of sB7-H3 in NSCLC-derived malignant pleural effusions (MPEs) and its clinical significance remain elusive., Methods: We measured and compared sB7-H3 levels in NSCLC-derived MPEs (n=52) and nonneoplastic pleural effusions (NPEs) (n=47), and then evaluated the diagnostic performance for sB7-H3 in NSCLC-derived MPEs. The correlation between MPE-derived sB7-H3 and clinical characteristics including TNM staging system was also analyzed., Results: The median value of sB7-H3 in 52 MPEs and 47 NPEs were 41.60ng/ml (interquartile range: 36.76-51.30ng/ml) and 31.55ng/ml (interquartile range: 26.97-36.63ng/ml) (P<0.0001), respectively. At the proposed cut-off value at 38.41ng/ml, sB7-H3 was capable of discriminating NSCLC-derived MPEs from NPEs with a sensitivity of 67.3% and a specificity of 91.5% respectively. Furthermore, MPEs-derived sB7-H3 was correlated with smoking status (P=0.005), primary tumor size (T factor, P=0.03), regional lymph node dissemination (N factor, P=0.019) and distant metastasis (M factor, P=0.009) of NSCLC patients., Conclusions: Upregulated sB7-H3 expression in MPEs is correlated with TNM stage of NSCLC and may serve as a potential biomarker for NSCLC-derived MPEs., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background: Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) is a widely expressed multi-functional adhesion molecule reported to serve as a serum biomarker in several types of cancer. However, the serum CEACAM1 expression in breast cancer is unclear. We investigated the serum concentrations of CEACAM1 in patients with breast cancer and determine the potential of serum CEACAM1 as a breast cancer biomarker., Methods: Serum specimens were obtained from 33 patients with breast cancer, 30 patients with benign breast diseases and 34 healthy donors. The serum CEACAM1 concentrations were examined by an enzyme-linked immunosorbent assay (ELISA)., Results: The serum CEACAM1 concentrations in the malignant group (532 ng/ml) were significantly higher than those of the benign group (423 ng/ml) and healthy control group (386 ng/ml) (both p<0.001). Based on univariable logistic regression, serum CEACAM1 concentrations significantly predicted breast cancer versus normal controls or benign breast diseases. Area under receiver operating characteristic curve (ROC) for serum CEACAM1 was 0.925(95% CI: 0.866-0.984). The optimal cut-off concentration of CEACAM1 was 475.82 ng/ml for discriminating breast cancer from normal controls., Conclusion: Serum concentrations of CEACAM1 may serve as a useful indicator for the presence of breast cancer., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Background: Tumor biomarkers are commonly used for cancer screening and as indicators of treatment effects. We recently reported that urine porphyrin levels from tumor-bearing mice were elevated compared with those from normal mice after administration of 5-aminolevulinic acid (ALA). In the present study, we evaluated the use of urine samples from bladder cancer patients as tumor biomarkers., Methods: ALA, 1.0 g, was orally administered to 66 bladder cancer patients and 20 healthy adults. The urine concentrations of uroporphyrin I (UPI), uroporphyrin III (UPIII), coproporphyrin I (CPI), coproporphyrin III (CPIII), and total porphyrins were measured using High Performance Liquid Chromatography (HPLC) system., Results: Almost all of the urinary porphyrin concentrations from the patients with bladder cancer were higher than those from healthy adults. Moreover, 8h after ALA administration, urinary UPI and CPI showed high sensitivity (100 for UPI and CPI) and specificity (96.4 for UPI and 91.4 for CPI)., Conclusion: These results indicate that the presence of urinary porphyrins after administration of ALA may function as tumor biomarkers. This method represents a possible new tumor screening method called photodynamic screening (PDS) using ALA-induced porphyrins., (Copyright © 2013 Elsevier B.V. All rights reserved.)