{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T18:27:58Z","timestamp":1786559278266,"version":"build-2736575974"},"reference-count":32,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T00:00:00Z","timestamp":1786492800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100016003","name":"Istanbul \u00dcniversitesi-Cerrahpasa","doi-asserted-by":"publisher","award":["35156"],"award-info":[{"award-number":["35156"]}],"id":[{"id":"10.13039\/501100016003","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Tubitak","award":["2224-A"],"award-info":[{"award-number":["2224-A"]}]},{"name":"T.C. Istanbul Yeni Yuzyil University"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>\n                    Silencing of the\n                    <jats:italic>Cysteine dioxygenase-1 (CDO1)<\/jats:italic>\n                    tumor suppressor gene by aberrant DNA methylation contributes to gastric carcinogenesis. Despite evidence that\n                    <jats:italic>Helicobacter pylori (H. pylori)<\/jats:italic>\n                    infection induces aberrant DNA methylation in the gastric mucosa,\n                    <jats:italic>CDO1<\/jats:italic>\n                    promoter methylation has not been well characterized in\n                    <jats:italic>H. Pylori<\/jats:italic>\n                    positive (HPP) patients with chronic gastritis. This study aimed to investigate the\n                    <jats:italic>CDO1<\/jats:italic>\n                    promoter methylation levels in patients with chronic gastritis with and without\n                    <jats:italic>H. pylori<\/jats:italic>\n                    infection, in comparison with gastric tumors. The quantitative analysis of\n                    <jats:italic>CDO1<\/jats:italic>\n                    promoter methylation and\n                    <jats:italic>CDO1<\/jats:italic>\n                    immunopositivity was performed in 45 primary gastric tumors, 17 biopsy samples of HPP chronic gastritis, 23\n                    <jats:italic>H. Pylori<\/jats:italic>\n                    negative (HPN) chronic gastritis, and 15 normal gastric mucosa samples (control group).\n                    <jats:italic>CDO1<\/jats:italic>\n                    expression was evaluated by immunohistochemistry, and promoter methylation levels were determined using quantitative methylation-specific PCR following bisulfite conversion.\n                    <jats:italic>CDO1<\/jats:italic>\n                    promoter methylation levels were significantly higher in the gastric cancer (GC) group compared to the HPN chronic gastritis and control groups (p\u2009&lt;\u20090.001). No significant difference was observed between the GC and HPP chronic gastritis groups. However,\n                    <jats:italic>CDO1<\/jats:italic>\n                    promoter methylation levels were significantly higher in the HPP group compared to the HPN group (p\u2009=\u20090.049). No significant differences in\n                    <jats:italic>CDO1<\/jats:italic>\n                    immunopositivity were observed among the study groups. ROC analysis demonstrated good discriminative ability of\n                    <jats:italic>CDO1<\/jats:italic>\n                    methylation between GC and non-cancer cases (AUC\u2009=\u20090.83), whereas its performance was more limited in distinguishing GC from HPP chronic gastritis (AUC\u2009=\u20090.67).\n                    <jats:italic>CDO1<\/jats:italic>\n                    promoter methylation is increased in GC and HPP chronic gastritis, suggesting that\n                    <jats:italic>H. pylori<\/jats:italic>\n                    -associated chronic inflammation may be associated with early epigenetic alterations. Although no direct correlation with protein expression was observed, our findings suggest that while\n                    <jats:italic>CDO1<\/jats:italic>\n                    methylation may be informative for identifying cancer-related epigenetic changes, it may be insufficient as a standalone biomarker in high-risk inflammatory conditions. Further studies are needed to clarify its clinical utility, particularly in high-risk populations.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0335832","type":"journal-article","created":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T17:34:02Z","timestamp":1786556042000},"page":"e0335832","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["A comparative study of CDO1 promoter methylation in gastric cancer and H. pylori-associated chronic gastritis: Implications for diagnostic performance"],"prefix":"10.1371","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2364-9139","authenticated-orcid":true,"given":"Selin","family":"Kankaya","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Metehan","family":"Karatas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Engin","family":"Hatipoglu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nuray","family":"Kepil","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zulal","family":"Kaptan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeynep","family":"Caliskan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matem","family":"Tuncdemir","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yildiz","family":"Dincer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,8,12]]},"reference":[{"issue":"3","key":"pone.0335832.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"},{"issue":"3","key":"pone.0335832.ref002","first-page":"71","article-title":"Chronic gastritis and cancer of the stomach","volume":"41","author":"IL Butov","year":"1979","journal-title":"Arkh Patol"},{"issue":"2","key":"pone.0335832.ref003","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/S1535-6108(04)00033-9","article-title":"Focus on gastric cancer","volume":"5","author":"T Ushijima","year":"2004","journal-title":"Cancer Cell"},{"issue":"15","key":"pone.0335832.ref004","doi-asserted-by":"crossref","first-page":"2214","DOI":"10.3748\/wjg.v13.i15.2214","article-title":"Hypermethylation and aberrant expression of Wnt antagonist secreted frizzled-related protein 1 in gastric cancer","volume":"13","author":"C-H Zhao","year":"2007","journal-title":"World J 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Kojima","year":"2019","journal-title":"Oncotarget"},{"issue":"6","key":"pone.0335832.ref008","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1007\/s00535-024-02094-y","article-title":"Severe induction of aberrant DNA methylation by nodular gastritis in adults","volume":"59","author":"A Sasaki","year":"2024","journal-title":"J Gastroenterol"},{"issue":"10","key":"pone.0335832.ref009","doi-asserted-by":"crossref","first-page":"5370","DOI":"10.1172\/JCI124070","article-title":"TET repression and increased DNMT activity synergistically induce aberrant DNA methylation","volume":"130","author":"H Takeshima","year":"2020","journal-title":"J Clin Invest"},{"issue":"3","key":"pone.0335832.ref010","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1007\/s00535-021-01848-2","article-title":"Autoimmune gastritis induces aberrant DNA methylation reflecting its carcinogenic potential","volume":"57","author":"C Takeuchi","year":"2022","journal-title":"J Gastroenterol"},{"issue":"3","key":"pone.0335832.ref011","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1136\/gutjnl-2014-307094","article-title":"Demonstration of the usefulness of epigenetic cancer risk prediction by a multicentre prospective cohort study","volume":"64","author":"K Asada","year":"2015","journal-title":"Gut"},{"issue":"4","key":"pone.0335832.ref012","doi-asserted-by":"crossref","first-page":"918","DOI":"10.3390\/biomedicines12040918","article-title":"The role of Cdo1 in Ferroptosis and Apoptosis in cancer","volume":"12","author":"X Chen","year":"2024","journal-title":"Biomedicines"},{"issue":"3","key":"pone.0335832.ref013","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1016\/j.gendis.2021.12.023","article-title":"Cysteine dioxygenase type 1 (CDO1): Its functional role in physiological and pathophysiological processes","volume":"10","author":"M Chen","year":"2022","journal-title":"Genes 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Compare","year":"2011","journal-title":"J Clin Pathol"},{"issue":"2","key":"pone.0335832.ref022","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1007\/s10120-020-01117-w","article-title":"Promising aberrant DNA methylation marker to predict gastric cancer development in individuals with family history and long-term effects of H. pylori eradication on DNA methylation","volume":"24","author":"HJ Kim","year":"2021","journal-title":"Gastric Cancer"},{"issue":"9","key":"pone.0335832.ref023","doi-asserted-by":"crossref","first-page":"9788","DOI":"10.18632\/oncotarget.7125","article-title":"Helicobacter pylori CagA induces tumor suppressor gene hypermethylation by upregulating DNMT1 via AKT-NF\u03baB pathway in gastric cancer development","volume":"7","author":"B Zhang","year":"2016","journal-title":"Oncotarget"},{"issue":"1","key":"pone.0335832.ref024","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1038\/s41419-025-08042-9","article-title":"Helicobacter pylori-induced 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dioxygenase type 1 (CDO1) gene promoter methylation during the adenoma-carcinoma sequence in colorectal cancer","volume":"13","author":"K Kojima","year":"2018","journal-title":"PLoS One"},{"issue":"1","key":"pone.0335832.ref028","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1515\/oncologie-2024-0324","article-title":"Histone methylation and acetylation in cancer: mechanism, progression, and targets","volume":"27","author":"S Bu","year":"2024","journal-title":"Oncologie"},{"key":"pone.0335832.ref029","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1042\/BJ20051510","article-title":"Regulation of cysteine dioxygenase degradation is mediated by intracellular cysteine levels and the ubiquitin-26 S proteasome system in the living rat","volume":"394","author":"JE Dominy","year":"2006","journal-title":"Biochem J"},{"issue":"1","key":"pone.0335832.ref030","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1186\/s12920-020-0657-6","article-title":"DNA hypermethylation 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