{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T00:31:36Z","timestamp":1760661096123,"version":"build-2065373602"},"reference-count":38,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2025,10,16]],"date-time":"2025-10-16T00:00:00Z","timestamp":1760572800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JSPS KAKENHI Grant Number JP20K09184"],"award-info":[{"award-number":["JSPS KAKENHI Grant Number JP20K09184"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JSPS KAKENHI Grant Number JP24K12309"],"award-info":[{"award-number":["JSPS KAKENHI Grant Number JP24K12309"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>Approximately 15% of patients with resected pathological stage IA lung adenocarcinoma develop recurrent disease, indicating the formation of a cancer metastasis-promoting microenvironment, and highlighting the importance of identifying early prognostic biomarkers. The MECA-79 epitope is a glycan structure modulating immune response, normally expressed on high endothelial venules. Ectopic MECA-79 expression has been recently reported in several cancer cells and is associated with poor prognosis. In this retrospective cohort study, we aimed to investigate the clinical and pathological significance of tumoral MECA-79 expression in early-stage lung cancer. Immunohistochemical analysis for MECA-79 was performed in 195 patients with pathological stage IA lung adenocarcinoma undergoing lobectomy. Clinical, radiological, and pathological factors were assessed, and recurrence-free survival (RFS) was analyzed using Kaplan\u2013Meier analysis and univariable Cox regression proportional hazards models. Multivariable Cox analyses were performed as exploratory analyses only due to the limited number of recurrence events. Tumoral MECA-79 expression was observed in 5.1% of cases (n\u2009=\u200910). Patients with MECA-79<jats:sup>+<\/jats:sup> tumor cells exhibited a larger pathological invasive size (2.1 vs. 1.6\u2009cm, <jats:italic><jats:italic>P<\/jats:italic>\u2009<\/jats:italic>=\u20090.044), higher rates of vascular invasion (90.0% vs. 40.0%, <jats:italic><jats:italic>P<\/jats:italic>\u2009<\/jats:italic>=\u20090.0023), and increased 5-year postoperative recurrence (40.0% vs. 7.6%, <jats:italic><jats:italic>P<\/jats:italic>\u2009<\/jats:italic>=\u20090.0061). Kaplan\u2013Meier analysis demonstrated significantly worse RFS for patients with MECA-79<jats:sup>+<\/jats:sup> tumor cells (5-year rate: 54.9% vs. 87.4%, <jats:italic><jats:italic>P<\/jats:italic>\u2009<\/jats:italic>=\u20090.003). The univariate Cox regression model identified body mass index, histological grade based on the International Association for the Study of Lung Cancer histological grading system, vascular invasion, spread through air spaces, and the presence of MECA-79<jats:sup>+<\/jats:sup> tumor cells as prognostic factors. Our results indicate that tumoral MECA-79 expression is associated with the recurrence of resected pathological stage IA lung adenocarcinoma; however, these findings should be validated in multicenter, stage-matched cohorts.<\/jats:p>","DOI":"10.1371\/journal.pone.0323233","type":"journal-article","created":{"date-parts":[[2025,10,16]],"date-time":"2025-10-16T17:37:31Z","timestamp":1760636251000},"page":"e0323233","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Clinical and pathological implications of the presence of MECA-79-expressing tumor cells in pathological stage IA lung adenocarcinoma"],"prefix":"10.1371","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5248-5343","authenticated-orcid":true,"given":"Tomohito","family":"Saito","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mitsuaki","family":"Ishida","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomoya O.","family":"Akama","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shiho","family":"Hattori","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Natsumi","family":"Maru","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takahiro","family":"Utsumi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aki K.","family":"Kobayashi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kento J.","family":"Fukumoto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroshi","family":"Matsui","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yohei","family":"Taniguchi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshinobu","family":"Hirose","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katsuyasu","family":"Kouda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomohiro","family":"Murakawa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2025,10,16]]},"reference":[{"issue":"3","key":"pone.0323233.ref001","first-page":"229","article-title":"Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"74","author":"F Bray","year":"2024","journal-title":"CA Cancer J Clin"},{"key":"pone.0323233.ref002","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1007\/s11748-023-01997-6","article-title":"Thoracic and cardiovascular surgeries in Japan during 2021: Annual report by the Japanese Association for Thoracic Surgery","volume":"72","author":"Committee for Scientific Affairs, The Japanese Association for Thoracic Surgery","year":"2024","journal-title":"Gen Thorac Cardiovasc Surg"},{"issue":"2","key":"pone.0323233.ref003","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1016\/j.jtho.2018.10.002","article-title":"Demographics, Safety and Quality, and Prognostic Information in Both the Seventh and Eighth Editions of the TNM Classification in 18,973 Surgical Cases of the Japanese Joint Committee of Lung Cancer Registry Database in 2010","volume":"14","author":"J Okami","year":"2019","journal-title":"J Thorac 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Uchimura","year":"2005","journal-title":"Nat Immunol"},{"key":"pone.0323233.ref023","first-page":"9150","article-title":"Beta 1,4-galactosyltransferase (beta 4GalT)-IV is specific for GlcNAc 6-O-sulfate. Beta 4GalT-IV acts on keratan sulfate-related glycans and a precursor glycan of 6-sulfosialyl-Lewis X","volume":"278","author":"A Seko","year":"2003","journal-title":"J Biol Chem"},{"key":"pone.0323233.ref024","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1016\/j.xjon.2022.03.004","article-title":"Survival after recurrence following surgical resected non-small cell lung cancer: A multicenter, prospective cohort study","volume":"10","author":"T Takenaka","year":"2022","journal-title":"JTCVS Open"},{"issue":"1","key":"pone.0323233.ref025","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pcbi.1002813","article-title":"Integration of the transcriptome and glycome for identification of glycan cell signatures","volume":"9","author":"SV Bennun","year":"2013","journal-title":"PLoS Comput Biol"},{"key":"pone.0323233.ref026","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/j.sbi.2016.09.013","article-title":"Multi-level regulation of cellular glycosylation: from genes to transcript to enzyme to structure","volume":"40","author":"S Neelamegham","year":"2016","journal-title":"Curr Opin Struct Biol"},{"key":"pone.0323233.ref027","doi-asserted-by":"crossref","first-page":"28","DOI":"10.3389\/fonc.2014.00028","article-title":"Altered tumor-cell glycosylation promotes metastasis","volume":"4","author":"I H\u00e4uselmann","year":"2014","journal-title":"Front Oncol"},{"issue":"9","key":"pone.0323233.ref028","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1111\/jop.12585","article-title":"Role of sialyl 6-sulfo Lewis X in antitumor immunity against oral squamous cell carcinoma","volume":"46","author":"H Yoshida","year":"2017","journal-title":"J Oral Pathol Med"},{"issue":"9","key":"pone.0323233.ref029","first-page":"7647","article-title":"GJB3: a comprehensive biomarker in pan-cancer prognosis and immunotherapy prediction","volume":"16","author":"J Zeng","year":"2024","journal-title":"Aging (Albany NY)"},{"issue":"7","key":"pone.0323233.ref030","doi-asserted-by":"crossref","DOI":"10.1042\/BSR20193468","article-title":"KRT8 and KRT19, associated with EMT, are hypomethylated and overexpressed in lung adenocarcinoma and link to unfavorable prognosis","volume":"40","author":"W Wang","year":"2020","journal-title":"Biosci Rep"},{"key":"pone.0323233.ref031","article-title":"Expression and prognostic analyses of ITGA11, ITGB4 and ITGB8 in human non-small cell lung cancer","volume":"7","author":"P Wu","year":"2019","journal-title":"PeerJ"},{"issue":"8","key":"pone.0323233.ref032","doi-asserted-by":"crossref","first-page":"1341","DOI":"10.1038\/cdd.2014.228","article-title":"LAMC2 enhances the metastatic potential of lung adenocarcinoma","volume":"22","author":"YW Moon","year":"2015","journal-title":"Cell Death Differ"},{"issue":"3","key":"pone.0323233.ref033","doi-asserted-by":"crossref","first-page":"1137","DOI":"10.3892\/or.2015.4082","article-title":"Prognostic implication of PTPRH hypomethylation in non-small cell lung cancer","volume":"34","author":"T Sato","year":"2015","journal-title":"Oncol Rep"},{"key":"pone.0323233.ref034","doi-asserted-by":"crossref","first-page":"106818","DOI":"10.1016\/j.phrs.2023.106818","article-title":"Targeting the KRT16-vimentin axis for metastasis in lung cancer","volume":"193","author":"W Wang","year":"2023","journal-title":"Pharmacol Res"},{"issue":"20","key":"pone.0323233.ref035","doi-asserted-by":"crossref","first-page":"12533","DOI":"10.3390\/ijms232012533","article-title":"Lipid Droplets in Lung Cancers Are Crucial for the Cell Growth and Starvation Survival","volume":"23","author":"J Lung","year":"2022","journal-title":"Int J Mol Sci"},{"issue":"6","key":"pone.0323233.ref036","doi-asserted-by":"crossref","first-page":"822","DOI":"10.1038\/s41388-018-0471-1","article-title":"Gjb4 serves as a novel biomarker for lung cancer and promotes metastasis and chemoresistance via Src activation","volume":"38","author":"Y-P 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