ArticleCell death & disease2017
Specific detection of soluble EphA2 fragments in blood as a new biomarker for pancreatic cancer.
Article in Cell death & disease, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed.
- First-in-human EphA2-targeting PET imaging with the bicyclic radiotracer [European journal of nuclear medicine and molecular imaging · 2026Article
- Nonlinear Modeling Reveals Novel Associations Between Genetically Predicted Protein Levels and Pancreatic Cancer Risk.Molecular carcinogenesis · 2026Article
- Proteolytic EphA2 fragments cooperatively promote hepatocellular carcinoma progression.Cell death & disease · 2026Article
- RSK4 promotes the metastasis of clear cell renal cell carcinoma by activating RUNX1-mediated angiogenesis.Cancer biology & therapy · 2025Article
- Unveiling the therapeutic promise of EphA2 in glioblastoma: a comprehensive review.Discover oncology · 2024Review
- Erythropoietin-induced hepatocyte receptor A2 regulates effect of pyroptosis on gastrointestinal colorectal cancer occurrence and metastasis resistance.World journal of gastrointestinal oncology · 2024Review
- Proteome-wide association study and functional validation identify novel protein markers for pancreatic ductal adenocarcinoma.GigaScience · 2024Article
- Advances and current concepts on Eph receptors and ephrins in upper digestive tract cancers.Frontiers in oncology · 2024Review
- External validation of genetically predicted protein biomarkers for pancreatic cancer risk using aptamer-based plasma levels: A prospective analysis in the Atherosclerosis Risk in Communities Study.International journal of cancer · 2023Article
- EphA2 Proteolytic Fragment as a Sensitive Diagnostic Biomarker for Very Early-stage Pancreatic Ductal Carcinoma.Cancer research communications · 2023Article
- Effect of chimeric antigen receptor T cells against protease-activated receptor 1 for treating pancreatic cancer.BMC medicine · 2023Article
- The EPH/Ephrin System in Pancreatic Ductal Adenocarcinoma (PDAC): From Pathogenesis to Treatment.International journal of molecular sciences · 2023Review
- Proteolytic cleavage of membrane proteins by membrane type-1 MMP regulates cancer malignant progression.Cancer science · 2023Review
- Single-EV analysis (sEVA) of mutated proteins allows detection of stage 1 pancreatic cancer.Science advances · 2022Article
- Interplay between soluble CD74 and macrophage-migration inhibitory factor drives tumor growth and influences patient survival in melanoma.Cell death & disease · 2022Article
- The State-of-the-Art of Phase II/III Clinical Trials for Targeted Pancreatic Cancer Therapies.Journal of clinical medicine · 2021Review
- Diagnostic Value of Circulating Progranulin and Its Receptor EphA2 in Predicting the Atheroma Burden in Patients with Coronary Artery Disease.Disease markers · 2021Article
- Kinome Array Profiling of Patient-Derived Pancreatic Ductal Adenocarcinoma Identifies Differentially Active Protein Tyrosine Kinases.International journal of molecular sciences · 2020Article
- Associations between Genetically Predicted Blood Protein Biomarkers and Pancreatic Cancer Risk.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2020Article
- Engineering Chimeric Antigen Receptor T Cells against Immune Checkpoint Inhibitors PD-1/PD-L1 for Treating Pancreatic Cancer.Molecular therapy oncolytics · 2020Article
Corrections and comments
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Authors and funding
4 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Because membrane type 1-matrix metalloproteinase 1 (MT1-MMP) and erythropoietin-producing hepatocellular receptor 2 (EphA2) expression are upregulated by the Ras/mitogen-activated protein kinase pathway, they are frequently coexpressed in malignant tumors. MT1-MMP cleaves the N-terminal ligand-binding domain of EphA2 and inactivates its ligand-dependent tumor-suppressing activity. Therefore, specific detection of the cleaved N-terminal EphA2 fragment in blood might be an effective biomarker to diagnose malignant tumors. To evaluate this possibility, we developed three monoclonal antibodies against the soluble EphA2 fragment. One of them recognized this fragment specifically, with negligible cross-reactivity to the intact form. We used the cleaved form-specific antibody to develop a quantitative enzyme-linked immunosorbent assay and confirmed the linear reactivity to the recombinant fragment. We applied this assay on commercially available serum specimens obtained from patients with several types of cancer including gastric, pancreatic, esophageal, gastroesophageal, and head-and-neck cancers, and healthy donors. Soluble EphA2 fragment levels in cancer-patient sera were higher than those in healthy donors (n=50). In particular, levels of eight out of nine (89%) pancreatic cancer patients and ten out of seventeen (59%) gastric cancer patients significantly exceeded cutoff values obtained from the healthy donors, whereas those of esophageal and head-and-neck cancer-patient sera were low. The preliminary receiver operating characteristic curve analysis for pancreatic cancer demonstrated that the sensitivity and specificity were 89.0% and 90.0%, respectively, whereas those of the conventional digestive tumor marker CA19-9 were 88.9% and 72.0%, respectively. These results indicated that specific detection of soluble EphA2 fragment levels in serum could be potentially useful as a biomarker to diagnose pancreatic cancer.
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