{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T06:03:57Z","timestamp":1789365837504,"version":"build-2803163510"},"reference-count":66,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T00:00:00Z","timestamp":1789344000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Pancreatic cancer (PC) remains an aggressive malignancy with poor clinical outcomes, underscoring the need for novel biomarkers to monitor patients. Immune checkpoint molecules [programmed death ligand 1 (PD-L1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4)] have been detected in CTCs, and their expression is associated with poor prognosis. Overexpression of STIM1 and ORAI1, core regulators of calcium signaling, and the amino acid transporter chaperone CD98hc, have been shown to enhance cancer cell survival and migration. This study evaluated the expression of these molecules in PC-CTCs, alongside cytokeratin (CK, tumor cell marker) and CD45 (pan leukocyte marker).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>CTCs were isolated from 40 patients using Ficoll density gradient centrifugation and characterized by immunofluorescence. Additionally, 15 were analyzed using the ISET platform. PBMCs from 10 healthy donors were also evaluated. Biomarker expression was assessed using the automated VyCAP platform, followed by ACCEPT software evaluation and statistical analysis of adjunct clinical data.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      CTCs were detected in 20% of patients, whereas all displayed (CK-\/CD45-) cells with tumor characteristics and nucleus size of \u226510 \u03bcm, designated as circulating tumor-associated cells (CTACs). CTACs were significantly elevated in patients compared to healthy donors, and ROC analysis demonstrated strong discriminative capacity (AUC = 0.9083). Similarly, using the ISET platform, CTCs were detected in 26.7% (4\/15), whereas CTACs were detected in 93.3% (14\/15). PD-L1-positive CTCs were identified in 2.5% of patients, while PD-L1 and CTLA-4 expression on CTACs was detected in 30% and 17.5% of patients, respectively. STIM1-positive and ORAI1-positive CTCs were observed in 15% and 2.5% of patients, while expression on CTACs was detected in 70% and 10% of patients. Concerning CD98hc, 32.5% of patients harbored (CD98hc+\/CD45-) cells. Interestingly, metastatic patients with PD-L1-positive CTCs exhibited shorter overall survival (OS;\n                      <jats:italic>p<\/jats:italic>\n                      = 0.025), while the presence of \u22652 (CD98hc+\/CD45-) cells among patients who progressed within 1 year was associated with shorter progression-free survival (PFS;\n                      <jats:italic>p<\/jats:italic>\n                      = 0.007). Conversely, the presence of STIM1-positive CTCs correlated with improved OS (\n                      <jats:italic>p<\/jats:italic>\n                      = 0.021).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>These findings provide a comprehensive characterization of CTCs and CTACs in PC using a multiplex biomarker panel associated with calcium signaling and immune checkpoint pathways, highlighting the pronounced heterogeneity and potential clinical relevance of these circulating cell populations.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcell.2026.1881239","type":"journal-article","created":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T05:38:49Z","timestamp":1789364329000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["The phenotypic heterogeneity of tumor-derived cells in the bloodstream of pancreatic cancer patients"],"prefix":"10.3389","volume":"14","author":[{"given":"Chrysoula","family":"Tagari","sequence":"first","affiliation":[{"name":"Laboratory of Biochemistry and Metastatic Signaling, Division of Genetics, Cell and Developmental Biology, Department of Biology, University of Patras","place":["Patras, Greece"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karolina","family":"Mangani","sequence":"additional","affiliation":[{"name":"Laboratory of Biochemistry and Metastatic Signaling, Division of Genetics, Cell and Developmental Biology, Department of Biology, University of Patras","place":["Patras, Greece"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Gogolides","sequence":"additional","affiliation":[{"name":"Laboratory of Biochemistry and Metastatic Signaling, Division of Genetics, Cell and Developmental Biology, Department of Biology, University of Patras","place":["Patras, Greece"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Argyro","family":"Roumeliotou","sequence":"additional","affiliation":[{"name":"Laboratory of Biochemistry and Metastatic Signaling, Division of Genetics, Cell and Developmental Biology, Department of Biology, University of Patras","place":["Patras, Greece"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Panagiota","family":"Golegou","sequence":"additional","affiliation":[{"name":"Laboratory of Biochemistry and Metastatic Signaling, Division of Genetics, Cell and Developmental Biology, Department of Biology, University of Patras","place":["Patras, Greece"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anastasia","family":"Xagara","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, General University Hospital of Larissa","place":["Larissa, Greece"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Filippos","family":"Koinis","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, General University Hospital of Larissa","place":["Larissa, Greece"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teresa","family":"Frisan","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Ume\u00e5 Centre for Microbial Research (UCMR), Ume\u00e5 University","place":["Ume\u00e5, Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ioannis S.","family":"Pateras","sequence":"additional","affiliation":[{"name":"Second Department of Pathology, \u201cAttikon\u201d University Hospital, Medical School, National and Kapodistrian University of Athens","place":["Athens, Greece"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophia N.","family":"Karagiannis","sequence":"additional","affiliation":[{"name":"St John\u2019s Institute of Dermatology, School of Basic and Medical Biosciences, & KHP Centre for Translational Medicine, Guy\u2019s Hospital, King\u2019s College London","place":["London, United Kingdom"]},{"name":"Breast Cancer Now Research Unit, School of Cancer & Pharmaceutical Sciences, King\u2019s College London, Innovation Hub, Guy\u2019s Hospital","place":["London, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Athanasios","family":"Kotsakis","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, General University Hospital of Larissa","place":["Larissa, Greece"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Galatea","family":"Kallergi","sequence":"additional","affiliation":[{"name":"Laboratory of Biochemistry and Metastatic Signaling, Division of Genetics, Cell and Developmental Biology, Department of Biology, University of Patras","place":["Patras, Greece"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,14]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1373\/clinchem.2012.194258","article-title":"Circulating tumor cells: liquid biopsy of cancer","volume":"59","author":"Alix-Panabi\u00e8res","year":"2013","journal-title":"Clin. Chem."},{"key":"B2","doi-asserted-by":"publisher","first-page":"858","DOI":"10.1158\/2159-8290.CD-20-1311","article-title":"Liquid biopsy: from discovery to clinical application","volume":"11","author":"Alix-Panabi\u00e8res","year":"2021","journal-title":"Cancer Discov."},{"key":"B3","doi-asserted-by":"publisher","first-page":"4681","DOI":"10.1158\/0008-5472.CAN-15-1633","article-title":"Identification of cancer-associated fibroblasts in circulating blood from patients with metastatic breast cancer","volume":"75","author":"Ao","year":"2015","journal-title":"Cancer Res."},{"key":"B4","doi-asserted-by":"publisher","first-page":"2271","DOI":"10.7150\/jca.70500","article-title":"Expression of CD98hc in pancreatic cancer and its role in cancer cell behavior","volume":"13","author":"Bianconi","year":"2022","journal-title":"J. Cancer"},{"key":"B5","doi-asserted-by":"publisher","first-page":"2057","DOI":"10.1093\/annonc\/mdt176","article-title":"Circulating tumor cells in locally advanced pancreatic adenocarcinoma: the ancillary CirCe 07 study to the LAP 07 trial","volume":"24","author":"Bidard","year":"2013","journal-title":"Ann. Oncol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"17163","DOI":"10.3748\/wjg.v20.i45.17163","article-title":"Circulating tumor cells in pancreatic cancer patients: enrichment and cultivation","volume":"20","author":"Bobek","year":"2014","journal-title":"World J. Gastroenterology"},{"key":"B7","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1097\/COC.0000000000000239","article-title":"CTLA-4 and PD-1 pathways: similarities, differences, and implications of their inhibition","volume":"39","author":"Buchbinder","year":"2016","journal-title":"Am. J. Clin. Oncol."},{"key":"B8","doi-asserted-by":"publisher","first-page":"294","DOI":"10.3390\/diagnostics12020294","article-title":"Evaluation of MMR status and PD-L1 expression using specimens obtained by EUS-FNB in patients with pancreatic ductal adenocarcinoma (PDAC)","volume":"12","author":"Constantin","year":"2022","journal-title":"Diagnostics"},{"key":"B9","doi-asserted-by":"publisher","first-page":"143","DOI":"10.21608\/jcbr.2021.56525.1108","article-title":"The expression of immune checkpoint inhibitors PD-L1 and CTLA-4 in pancreatic versus non-pancreatic periampullary adenocarcinoma: an immunohistochemical study","volume":"5","author":"El-Anwar","year":"2021","journal-title":"Egypt. J. Cancer Biomed. Res."},{"key":"B10","doi-asserted-by":"publisher","first-page":"189420","DOI":"10.1016\/j.bbcan.2025.189420","article-title":"STIM1-mediated calcium signalling in cancer: its relation to tumour aggressiveness and therapeutic Horizons","volume":"1880","author":"Fang","year":"2025","journal-title":"Biochimica Biophysica Acta Rev. Cancer"},{"key":"B11","doi-asserted-by":"publisher","first-page":"2266","DOI":"10.3390\/cells12182266","article-title":"Circulating tumor cell subpopulations predict treatment outcome in pancreatic ductal adenocarcinoma (PDAC) patients","volume":"12","author":"Freed","year":"2023","journal-title":"Cells"},{"key":"B12","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1016\/j.hbpd.2018.03.007","article-title":"The clinicopathological and prognostic significance of PD-L1 expression in pancreatic cancer: a meta-analysis","volume":"17","author":"Gao","year":"2018","journal-title":"Hepatobiliary & Pancreat. Dis. Int."},{"key":"B13","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1186\/s13046-016-0340-0","article-title":"Clinical significance of pancreatic circulating tumor cells using combined negative enrichment and immunostaining-fluorescence in situ hybridization","volume":"35","author":"Gao","year":"2016","journal-title":"J. Exp. & Clin. Cancer Res."},{"key":"B14","doi-asserted-by":"publisher","first-page":"178","DOI":"10.1186\/1471-2407-12-178","article-title":"Circulating tumour cells escape from EpCAM-based detection due to epithelial-to-mesenchymal transition","volume":"12","author":"Gorges","year":"2012","journal-title":"BMC Cancer"},{"key":"B15","doi-asserted-by":"publisher","first-page":"485","DOI":"10.3390\/cancers13030485","article-title":"Preoperative CTC-detection by CellSearch\u00ae is associated with early distant metastasis and impaired survival in resected pancreatic cancer","volume":"13","author":"Hugenschmidt","year":"2021","journal-title":"Cancers (Basel)"},{"key":"B16","doi-asserted-by":"publisher","first-page":"589","DOI":"10.1136\/jclinpath-2020-206457","article-title":"Prognostic values of L-type amino acid transporter 1 and CD98hc expression in breast cancer","volume":"74","author":"Ichinoe","year":"2021","journal-title":"J. Clin. Pathology"},{"key":"B17","doi-asserted-by":"publisher","first-page":"3473","DOI":"10.1245\/s10434-009-0685-0","article-title":"CD98 expression is associated with poor prognosis in resected non-small-cell lung cancer with lymph node metastases","volume":"16","author":"Kaira","year":"2009","journal-title":"Ann. Surg. Oncol."},{"key":"B18","doi-asserted-by":"publisher","first-page":"632","DOI":"10.1038\/bjc.2012.310","article-title":"Prognostic significance of L-type amino-acid transporter 1 expression in surgically resected pancreatic cancer","volume":"107","author":"Kaira","year":"2012","journal-title":"Br. J. Cancer"},{"key":"B19","doi-asserted-by":"publisher","first-page":"1758834017750121","DOI":"10.1177\/1758834017750121","article-title":"Evaluation of PD-L1\/PD-1 on circulating tumor cells in patients with advanced non-small cell lung cancer","volume":"10","author":"Kallergi","year":"2018","journal-title":"Ther. Adv. Med. Oncol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"508","DOI":"10.1038\/bjc.2011.545","article-title":"A pilot study to explore circulating tumour cells in pancreatic cancer as a novel biomarker","volume":"106","author":"Khoja","year":"2012","journal-title":"Br. J. Cancer"},{"key":"B21","doi-asserted-by":"publisher","first-page":"750","DOI":"10.3390\/cancers12030750","article-title":"Calcium release-activated calcium (CRAC) channel inhibition suppresses pancreatic ductal adenocarcinoma cell proliferation and patient-derived tumor growth","volume":"12","author":"Khan","year":"2020","journal-title":"Cancers"},{"key":"B22","doi-asserted-by":"publisher","first-page":"2263","DOI":"10.1016\/j.bbamcr.2014.02.012","article-title":"Orai1 and STIM1 mediate SOCE and contribute to apoptotic resistance of pancreatic adenocarcinoma","volume":"1843","author":"Kondratska","year":"2014","journal-title":"Biochimica Biophysica Acta Mol. Cell Res."},{"key":"B23","doi-asserted-by":"publisher","first-page":"1623","DOI":"10.1002\/1878-0261.12537","article-title":"Liquid biopsy in pancreatic ductal adenocarcinoma: current status of circulating tumor cells and circulating tumor DNA","volume":"13","author":"Lee","year":"2019","journal-title":"Mol. Oncol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"1206565","DOI":"10.3389\/fonc.2023.1206565","article-title":"Phenotypic characteristics of circulating tumor cells and predictive impact for efficacy of chemotherapy in patients with pancreatic cancer: a prospective study","volume":"13","author":"Lee","year":"2023","journal-title":"Front. Oncol."},{"key":"B25","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1186\/s13000-017-0678-4","article-title":"PD-L1 in pancreatic ductal adenocarcinoma: a retrospective analysis of 373 Chinese patients using an in vitro diagnostic assay","volume":"13","author":"Liang","year":"2018","journal-title":"Diagn. Pathol."},{"key":"B26","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1002\/gcc.22695","article-title":"Liquid biopsies","volume":"58","author":"Lianidou","year":"2019","journal-title":"Genes, Chromosomes & Cancer"},{"key":"B27","doi-asserted-by":"publisher","first-page":"3047","DOI":"10.3892\/mmr.2015.3778","article-title":"Effects of stromal interacting molecule 1 gene silencing by short hairpin RNA on the biological behavior of human gastric cancer cells","volume":"12","author":"Liu","year":"2015","journal-title":"Mol. Med. Rep."},{"key":"B28","doi-asserted-by":"publisher","first-page":"806","DOI":"10.3390\/cancers11060806","article-title":"PD-L1 expression with epithelial mesenchymal transition of circulating tumor cells is associated with poor survival in curatively resected non-small cell lung cancer","volume":"11","author":"Manjunath","year":"2019","journal-title":"Cancers"},{"key":"B29","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1016\/j.jconrel.2024.07.023","article-title":"Enhancing pancreatic cancer immunotherapy: leveraging localized delivery strategies through the use of implantable devices and scaffolds","volume":"373","author":"Minaei","year":"2024","journal-title":"J. Control. Release"},{"key":"B30","doi-asserted-by":"publisher","first-page":"4169","DOI":"10.3390\/cancers15164169","article-title":"Improved characterization of circulating tumor cells and cancer-associated fibroblasts in one-tube assay in breast cancer patients using imaging flow cytometry","volume":"15","author":"Muchli\u0144ska","year":"2023","journal-title":"Cancers"},{"key":"B31","doi-asserted-by":"publisher","first-page":"757","DOI":"10.1042\/BJ20150364","article-title":"Epithelial-mesenchymal transition, IP3 receptors and ER-PM junctions: translocation of Ca2+ signalling complexes and regulation of migration","volume":"473","author":"Okeke","year":"2016","journal-title":"Biochem. J."},{"key":"B32","doi-asserted-by":"publisher","first-page":"2158","DOI":"10.3390\/cancers13092158","article-title":"Clinical relevance of mesenchymal- and stem-associated phenotypes in circulating tumor cells isolated from lung cancer patients","volume":"13","author":"Pantazaka","year":"2021","journal-title":"Cancers"},{"key":"B33","doi-asserted-by":"publisher","first-page":"102109","DOI":"10.1016\/j.jsps.2024.102109","article-title":"Role of KDM2B epigenetic factor in regulating calcium signaling in prostate cancer cells","volume":"32","author":"Pantazaka","year":"2024","journal-title":"Saudi Pharm. J."},{"key":"B34","doi-asserted-by":"publisher","first-page":"2038","DOI":"10.1002\/1878-0261.13765","article-title":"Integrative analysis of circulating tumor cells (CTCs) and exosomes from small-cell lung cancer (SCLC) patients: a comprehensive approach","volume":"19","author":"Papakonstantinou","year":"2025","journal-title":"Mol. Oncol."},{"key":"B35","doi-asserted-by":"publisher","first-page":"1557","DOI":"10.14670\/HH-18-749","article-title":"The role of CD98 heavy chain in cancer development","volume":"39","author":"Park","year":"2024","journal-title":"Histology Histopathol."},{"key":"B36","doi-asserted-by":"publisher","first-page":"e002140","DOI":"10.1136\/jitc-2020-002140","article-title":"Immunotherapy using IgE or CAR T cells for cancers expressing the tumor antigen SLC3A2","volume":"9","author":"Pellizzari","year":"2021","journal-title":"J. Immunother. Cancer."},{"key":"B37","doi-asserted-by":"publisher","first-page":"1073","DOI":"10.1097\/SLA.0000000000001600","article-title":"Circulating tumor cell phenotype predicts recurrence and survival in pancreatic adenocarcinoma","volume":"264","author":"Poruk","year":"2016","journal-title":"Ann. Surg."},{"key":"B38","doi-asserted-by":"publisher","first-page":"74015","DOI":"10.18632\/oncotarget.12187","article-title":"FGF4 induces epithelial-mesenchymal transition by inducing store-operated calcium entry in lung adenocarcinoma","volume":"7","author":"Qi","year":"2016","journal-title":"Oncotarget"},{"key":"B39","doi-asserted-by":"publisher","first-page":"408","DOI":"10.1038\/s41420-023-01703-8","article-title":"STIM1 in tumor cell death: Angel or devil?","volume":"9","author":"Ren","year":"2023","journal-title":"Cell Death Discov."},{"key":"B40","doi-asserted-by":"publisher","first-page":"101281","DOI":"10.1016\/j.gendis.2024.101281","article-title":"STIM1 promotes acquired resistance to sorafenib by attenuating ferroptosis in hepatocellular carcinoma","volume":"11","author":"Ren","year":"2024","journal-title":"Genes & Dis."},{"key":"B41","doi-asserted-by":"publisher","first-page":"349","DOI":"10.1016\/j.cell.2011.11.025","article-title":"EMT and dissemination precede pancreatic tumor formation","volume":"148","author":"Rhim","year":"2012","journal-title":"Cell"},{"key":"B42","doi-asserted-by":"publisher","first-page":"1399092","DOI":"10.3389\/fcell.2024.1399092","article-title":"STIM1, ORAI1, and KDM2B in circulating tumor cells (CTCs) isolated from prostate cancer patients","volume":"12","author":"Roumeliotou","year":"","journal-title":"Front. Cell Dev. Biol."},{"key":"B43","doi-asserted-by":"publisher","first-page":"782","DOI":"10.3390\/cells13090782","article-title":"Comprehensive analysis of CXCR4, JUNB, and PD-L1 expression in circulating tumor cells (CTCs) from prostate cancer patients","volume":"13","author":"Roumeliotou","year":"","journal-title":"Cells"},{"key":"B44","doi-asserted-by":"publisher","first-page":"1970","DOI":"10.1038\/s41416-021-01350-9","article-title":"Characterisation of circulating tumour cell phenotypes identifies a partial-EMT sub-population for clinical stratification of pancreatic cancer","volume":"124","author":"Semaan","year":"2021","journal-title":"Br. J. Cancer"},{"key":"B45","doi-asserted-by":"publisher","first-page":"616440","DOI":"10.3389\/fonc.2020.616440","article-title":"Detection of circulating tumor cells in resectable pancreatic ductal adenocarcinoma: a prospective evaluation as a prognostic marker","volume":"10","author":"Song","year":"2021","journal-title":"Front. Oncol."},{"key":"B46","doi-asserted-by":"publisher","first-page":"1182","DOI":"10.1016\/S0140-6736(25)00261-2","article-title":"Pancreatic cancer","volume":"405","author":"Stoop","year":"2025","journal-title":"Pancreat. Cancer. Lancet."},{"key":"B47","doi-asserted-by":"publisher","first-page":"1923","DOI":"10.1093\/annonc\/mdx206","article-title":"Prognostic significance of PD-L1 expression on circulating tumor cells in patients with head and neck squamous cell carcinoma","volume":"28","author":"Strati","year":"2017","journal-title":"Ann. Oncol."},{"key":"B48","doi-asserted-by":"publisher","first-page":"4138","DOI":"10.3390\/cancers13164138","article-title":"Pancreatic cancer and immunotherapy: a clinical overview","volume":"13","author":"Timmer","year":"2021","journal-title":"Cancers"},{"key":"B49","doi-asserted-by":"publisher","first-page":"1974","DOI":"10.3390\/cancers15071974","article-title":"Immune checkpoint and EMT-related molecules in circulating tumor cells (CTCs) from triple negative breast cancer patients and their clinical impact","volume":"15","author":"Vardas","year":"2023","journal-title":"Cancers"},{"key":"B50","doi-asserted-by":"publisher","first-page":"100","DOI":"10.20892\/j.issn.2095-3941.2018.0304","article-title":"STIM1 overexpression in hypoxia microenvironment contributes to pancreatic carcinoma progression","volume":"16","author":"Wang","year":"2019","journal-title":"Cancer Biol. & Med."},{"key":"B51","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1186\/s12943-023-01870-3","article-title":"Liquid biopsy techniques and pancreatic cancer: diagnosis, monitoring, and evaluation","volume":"22","author":"Wang","year":"2023","journal-title":"Mol. Cancer"},{"key":"B52","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1038\/s41698-017-0028-8","article-title":"Discrete microfluidics for the isolation of circulating tumor cell subpopulations targeting fibroblast activation protein alpha and epithelial cell adhesion molecule","volume":"1","author":"Witek","year":"2017","journal-title":"NPJ Precis. Oncol."},{"key":"B53","doi-asserted-by":"publisher","first-page":"1251100","DOI":"10.3389\/fonc.2023.1251100","article-title":"CD98 heavy chain as a prognostic biomarker and target for cancer treatment","volume":"13","author":"Xia","year":"2023","journal-title":"Front. Oncol."},{"key":"B54","doi-asserted-by":"publisher","first-page":"8115","DOI":"10.3390\/ijms21218115","article-title":"Fluid shear stress induces EMT of circulating tumor cells via JNK signaling in favor of their survival during hematogenous dissemination","volume":"21","author":"Xin","year":"2020","journal-title":"Int. J. Mol. Sci."},{"key":"B55","doi-asserted-by":"publisher","first-page":"5112","DOI":"10.1158\/1078-0432.CCR-16-3081","article-title":"The novel association of circulating tumor cells and circulating megakaryocytes with prostate cancer prognosis","volume":"23","author":"Xu","year":"2017","journal-title":"Clin. Cancer Res."},{"key":"B56","doi-asserted-by":"publisher","first-page":"726","DOI":"10.1007\/s10147-017-1112-3","article-title":"PD-L1 expression in pancreatic ductal adenocarcinoma is a poor prognostic factor in patients with high CD8+ tumor-infiltrating lymphocytes: highly sensitive detection using phosphor-integrated dot staining","volume":"22","author":"Yamaki","year":"2017","journal-title":"Int. J. Clin. Oncol."},{"key":"B57","doi-asserted-by":"publisher","first-page":"8231","DOI":"10.3892\/ol.2018.8437","article-title":"Knockdown of stromal interaction molecule 1 inhibits proliferation of colorectal cancer cells by inducing apoptosis","volume":"15","author":"Yang","year":"2018","journal-title":"Oncol. Lett."},{"key":"B58","doi-asserted-by":"publisher","first-page":"1217","DOI":"10.7150\/ijbs.56833","article-title":"3,3\u2032-Diindolylmethane induces gastric cancer cells death via STIM1 mediated store-operated calcium entry","volume":"17","author":"Ye","year":"2021","journal-title":"Int. J. Biol. Sci."},{"key":"B59","doi-asserted-by":"publisher","first-page":"217350","DOI":"10.1016\/j.canlet.2024.217350","article-title":"Frontiers in pancreatic cancer on biomarkers, microenvironment, and immunotherapy","volume":"610","author":"Yu","year":"2025","journal-title":"Cancer Lett."},{"key":"B60","doi-asserted-by":"publisher","first-page":"368","DOI":"10.1159\/000489917","article-title":"The epigenetic factor KDM2B regulates EMT and small GTPases in colon tumor cells","volume":"47","author":"Zacharopoulou","year":"2018","journal-title":"Cell. Physiology Biochem."},{"key":"B61","doi-asserted-by":"publisher","first-page":"e0186562","DOI":"10.1371\/journal.pone.0186562","article-title":"Quantifying HER-2 expression on circulating tumor cells by ACCEPT","volume":"12","author":"Zeune","year":"2017","journal-title":"PLoS One"},{"key":"B62","doi-asserted-by":"publisher","first-page":"1228","DOI":"10.1002\/ijc.29070","article-title":"Patterns of circulating tumor cells identified by CEP8, CK and CD45 in pancreatic cancer","volume":"136","author":"Zhang","year":"2015","journal-title":"Int. J. Cancer"},{"key":"B63","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1002\/cjp2.259","article-title":"PD-L1 and PD-L2 expression in pancreatic ductal adenocarcinoma and their correlation with immune infiltrates and DNA damage response molecules","volume":"8","author":"Zhang","year":"2022","journal-title":"J. Pathology Clin. Res."},{"key":"B64","doi-asserted-by":"publisher","first-page":"138","DOI":"10.3748\/wjg.v25.i1.138","article-title":"Molecular detection of epithelial-mesenchymal transition markers in circulating tumor cells from pancreatic cancer patients: potential role in clinical practice","volume":"25","author":"Zhao","year":"2019","journal-title":"World J. Gastroenterology"},{"key":"B65","doi-asserted-by":"publisher","first-page":"796","DOI":"10.21037\/hbsn-20-383","article-title":"Molecular characterization of circulating tumor cells in pancreatic ductal adenocarcinoma: potential diagnostic and prognostic significance in clinical practice","volume":"10","author":"Zhao","year":"2021","journal-title":"Hepatobiliary Surg. Nutr."},{"key":"B66","doi-asserted-by":"publisher","first-page":"188868","DOI":"10.1016\/j.bbcan.2023.188868","article-title":"Liquid biopsy in pancreatic cancer: current perspective and future outlook","volume":"1878","author":"Zhao","year":"2023","journal-title":"Biochimica Biophysica Acta Rev. Cancer"}],"container-title":["Frontiers in Cell and Developmental Biology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcell.2026.1881239\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T05:38:50Z","timestamp":1789364330000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcell.2026.1881239\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,14]]},"references-count":66,"alternative-id":["10.3389\/fcell.2026.1881239"],"URL":"https:\/\/doi.org\/10.3389\/fcell.2026.1881239","relation":{},"ISSN":["2296-634X"],"issn-type":[{"value":"2296-634X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,14]]},"article-number":"1881239"}}