{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T08:21:47Z","timestamp":1787732507535,"version":"build-2784847793"},"reference-count":20,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T00:00:00Z","timestamp":1787097600000},"content-version":"vor","delay-in-days":18,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["FASEB BioAdvances"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Gastric cancer often presents at advanced stages, limiting treatment outcomes. Circulating tumor cells (CTCs), particularly those undergoing epithelial\u2013mesenchymal transition (EMT), have emerged as promising biomarkers for real\u2010time disease monitoring. Using magnetic\u2010activated cell sorting (MACS), we enriched both epithelial (EpCAM\n                    <jats:sup>+<\/jats:sup>\n                    ) and mesenchymal (CD90\n                    <jats:sup>+<\/jats:sup>\n                    ) CTCs and evaluated the expression of the tumor\u2010suppressive microRNA miR\u201029b in CTCs of gastric cancer patients. This study aimed to explore the clinical relevance of perioperative CTC phenotypes and miR\u201029b as potential diagnostic and prognostic markers. We conducted a multi\u2010phase study integrating systematic review, bioinformatics, and experimental analyses to investigate CTC phenotypes and ECM\u2010associated gene expression in GC. Peripheral blood samples were collected from 30 treatment\u2010na\u00efve gastric cancer patients at two time points: before initiation of therapy and 1\u2009month after curative\u2010intent gastrectomy. Circulating tumor cells (CTCs) were isolated using CD45\u2010negative magnetic\u2010activated cell sorting (MACS). Immunofluorescence staining was performed to phenotype CTCs based on EpCAM (epithelial) and CD90 (mesenchymal) expression. Total RNA was extracted from tumor tissues and isolated CTCs to evaluate ECM\u2010related genes and miR\u201029b expression using quantitative real\u2010time PCR. Bioinformatics\u2010guided gene selection and statistical analysis were used to assess diagnostic and prognostic relevance. CTCs were detected in 83.3% (25\/30) of gastric cancer patients prior to treatment. Mesenchymal CTCs (CD90\n                    <jats:sup>+<\/jats:sup>\n                    ) were markedly more frequent than epithelial CTCs (EpCAM\n                    <jats:sup>+<\/jats:sup>\n                    ), with mean baseline counts of 14.07 versus 0.5 cells per 10\u2009mL of blood, respectively. Following gastrectomy and chemotherapy, mesenchymal CTCs significantly declined (mean: 1.18;\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.0064), while epithelial CTCs were nearly undetectable (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.0246). Based on perioperative CTC dynamics, patients were stratified into three risk groups: high\u2010risk (16%), intermediate\u2010risk (68%), and low\u2010risk (16%). All observed deaths occurred in the high\u2010risk group during 14\u2009months of follow\u2010up, with Kaplan\u2013Meier analysis showing significantly lower survival in this group (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.0107). Expression analysis revealed significant downregulation of miR\u201029b in tumor tissues (fold change\u2009=\u20090.5163;\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.0136) and in CTCs (fold change\u2009=\u20090.2049;\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.0001) compared to healthy controls. Although miR\u201029b levels were broadly downregulated in gastric cancer patients, no significant differences were observed among clinicopathological subgroups within the patient cohort. ROC analysis showed strong diagnostic performance of miR\u201029b in tissue (AUC\u2009=\u20090.883, 95% CI: 0.798\u20130.969), with 96.7% sensitivity and 70% specificity. CD90 serves as a sensitive mesenchymal marker for detecting CTCs that lack epithelial features, enabling more comprehensive identification of aggressive CTC phenotypes in gastric cancer. Moreover, the perioperative dynamics of CTCs\u2014especially postoperative increases\u2014provide a valuable tool for patient risk stratification and survival prediction. Importantly, our findings suggest that miR\u201029b expression in CTCs, together with perioperative CTC dynamics, may serve as a non\u2010invasive biomarker for monitoring disease progression and recurrence in gastric cancer.\n                  <\/jats:p>","DOI":"10.1096\/fba.2025-00314","type":"journal-article","created":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T15:40:14Z","timestamp":1787154014000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Integrated Molecular and Phenotypic Profiling of Circulating Tumor Cells in Gastric Cancer: A Translational Perspective"],"prefix":"10.1096","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1642-0483","authenticated-orcid":false,"given":"Mohammad Reza","family":"Eskandarion","sequence":"first","affiliation":[{"name":"Cancer Research Center, Cancer Institute, Imam Khomeini Hospital Complex Tehran University of Medical Sciences  Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharareh","family":"Eskandarieh","sequence":"additional","affiliation":[{"name":"Multiple Sclerosis Research Center, Neuroscience Institute Tehran University of Medical Sciences  Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abbas","family":"Shakoori Farahani","sequence":"additional","affiliation":[{"name":"Medical Genetics Ward, Imam Khomeini Hospital Complex Tehran University of Medical Sciences  Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farideh","family":"Ghanbari Mardasi","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics School of Medicine Tehran University of Medical Sciences  Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Habibollah","family":"Mahmoodzadeh","sequence":"additional","affiliation":[{"name":"Department of Surgery, Cancer Research Center, Cancer Institute, Imam Khomeini Hospital Complex Tehran University of Medical Sciences  Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kamran","family":"Roudini","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Hematology and Medical Oncology Ward, Cancer Research Center, Imam Khomeini Hospital Complex Tehran University of Medical Sciences, Cancer Institute  Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farhad","family":"Shahi","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Cancer Research Center, Cancer Institute, Imam Khomeini Hospital Complex Tehran University of Medical Sciences  Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad Ali","family":"Oghabian","sequence":"additional","affiliation":[{"name":"Medical Physics Department, Faculty of Medicine Tehran University of Medical Sciences  Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad","family":"Taher","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Imam Khomeini Hospital Complex Tehran University of Medical Sciences  Tehran Iran"},{"name":"Liver Transplantation Research Center Tehran University of Medical Sciences  Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reza","family":"Shirkoohi","sequence":"additional","affiliation":[{"name":"Cancer Research Center, Cancer Institute, Imam Khomeini Hospital Complex Tehran University of Medical Sciences  Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,19]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21660"},{"key":"e_1_2_10_3_1","unstructured":"Network NCC \u201cGastric Cancer. NCCN Clinical Practice Guidelines in Oncology \u201d(2023)."},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1373\/clinchem.2012.194258"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10238-024-01310-6"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1228522"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1245\/s10434-020-08827-6"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2024.e30253"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.29455"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0123976"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1593\/tlo.13271"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2015.09.006"},{"key":"e_1_2_10_13_1","first-page":"281","article-title":"MicroRNAs: Genomics, Biogenesis, Mechanism, and Function","volume":"166","author":"Bartel D.","year":"2014","journal-title":"Cell"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/nsmb.1533"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-017-0620-0"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2008.30"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-pathol-012513-104715"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature03702"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.28607"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1210436"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/embor.2009.9"}],"container-title":["FASEB BioAdvances"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/pdf\/10.1096\/fba.2025-00314","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/full-xml\/10.1096\/fba.2025-00314","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/pdf\/10.1096\/fba.2025-00314","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T08:00:08Z","timestamp":1787731208000},"score":1,"resource":{"primary":{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/10.1096\/fba.2025-00314"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8]]},"references-count":20,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2026,8]]}},"alternative-id":["10.1096\/fba.2025-00314"],"URL":"https:\/\/doi.org\/10.1096\/fba.2025-00314","archive":["Portico"],"relation":{},"ISSN":["2573-9832","2573-9832"],"issn-type":[{"value":"2573-9832","type":"print"},{"value":"2573-9832","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8]]},"assertion":[{"value":"2025-12-09","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-21","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-19","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70140"}}