{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T00:47:57Z","timestamp":1791852477515,"version":"4.3.4"},"reference-count":24,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T00:00:00Z","timestamp":1760313600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T00:00:00Z","timestamp":1760313600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Gastric Cancer"],"published-print":{"date-parts":[[2026,1]]},"DOI":"10.1007\/s10120-025-01674-y","type":"journal-article","created":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T05:32:24Z","timestamp":1760333544000},"page":"39-52","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Clinical utility impact of DNA-based cytology using droplet digital methylation-specific PCR in gastric cancer"],"prefix":"10.1007","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1983-4692","authenticated-orcid":false,"given":"Hiroki","family":"Harada","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takafumi","family":"Soeno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akira","family":"Ooki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kanako","family":"Naito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyuki","family":"Minoura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kota","family":"Okuno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shohei","family":"Fujita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikiko","family":"Sakuraya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tadashi","family":"Higuchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koshi","family":"Kumagai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeshi","family":"Naitoh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yusuke","family":"Kumamoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoki","family":"Hiki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keishi","family":"Yamashita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,10,13]]},"reference":[{"key":"1674_CR1","first-page":"209","volume":"71","author":"H Sung","year":"2021","unstructured":"Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71:209\u201349.","journal-title":"CA Cancer J Clin"},{"key":"1674_CR2","doi-asserted-by":"publisher","first-page":"958","DOI":"10.1002\/ags3.12835","volume":"8","author":"T Higashi","year":"2024","unstructured":"Higashi T, Kurokawa Y. Incidence, mortality, survival, and treatment statistics of cancers in digestive organs-Japanese cancer statistics 2024. Ann Gastroenterol Surg. 2024;8:958\u201365.","journal-title":"Ann Gastroenterol Surg"},{"key":"1674_CR3","doi-asserted-by":"publisher","first-page":"122","DOI":"10.1002\/ags3.12218","volume":"3","author":"K Hosoda","year":"2019","unstructured":"Hosoda K, Watanabe M, Yamashita K. Re-emerging role of macroscopic appearance in treatment strategy for gastric cancer. Ann Gastroenterol Surg. 2019;3:122\u20139.","journal-title":"Ann Gastroenterol Surg"},{"key":"1674_CR4","doi-asserted-by":"publisher","first-page":"1324","DOI":"10.1016\/j.ejso.2015.05.021","volume":"41","author":"K Yamashita","year":"2015","unstructured":"Yamashita K, Ushiku H, Katada N, Hosoda K, Moriya H, Mieno H, et al. Reduced preoperative serum albumin and absence of peritoneal dissemination may be predictive factors for long-term survival with advanced gastric cancer with positive cytology test. Eur J Surg Oncol. 2015;41:1324\u201332.","journal-title":"Eur J Surg Oncol"},{"key":"1674_CR5","doi-asserted-by":"publisher","first-page":"499","DOI":"10.1097\/00000658-200204000-00007","volume":"235","author":"Y Kodera","year":"2002","unstructured":"Kodera Y, Nakanishi H, Ito S, Yamamura Y, Kanemitsu Y, Shimizu Y, et al. Quantitative detection of disseminated free cancer cells in peritoneal washes with real-time reverse transcriptase-polymerase chain reaction: a sensitive predictor of outcome for patients with gastric carcinoma. Ann Surg. 2002;235:499\u2013506.","journal-title":"Ann Surg"},{"key":"1674_CR6","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0214872","volume":"14","author":"H Harada","year":"2019","unstructured":"Harada H, Hosoda K, Moriya H, Mieno H, Ema A, Ushiku H, et al. Cancer-specific promoter DNA methylation of Cysteine dioxygenase type 1 (CDO1) gene as an important prognostic biomarker of gastric cancer. PLoS ONE. 2019;14:e0214872.","journal-title":"PLoS ONE"},{"key":"1674_CR7","doi-asserted-by":"publisher","first-page":"3263","DOI":"10.1038\/onc.2010.76","volume":"29","author":"A Ooki","year":"2010","unstructured":"Ooki A, Yamashita K, Kikuchi S, Sakuramoto S, Katada N, Kokubo K, et al. Potential utility of HOP homeobox gene promoter methylation as a marker of tumor aggressiveness in gastric cancer. Oncogene. 2010;29:3263\u201375.","journal-title":"Oncogene"},{"key":"1674_CR8","doi-asserted-by":"publisher","first-page":"784","DOI":"10.1007\/s10120-017-0697-6","volume":"20","author":"H Ushiku","year":"2017","unstructured":"Ushiku H, Yamashita K, Ema A, Minatani N, Kikuchi M, Kojo K, et al. DNA diagnosis of peritoneal fluid cytology test by CDO1 promoter DNA hypermethylation in gastric cancer. Gastric Cancer. 2017;20:784\u201392.","journal-title":"Gastric Cancer"},{"key":"1674_CR9","doi-asserted-by":"publisher","first-page":"2846","DOI":"10.1111\/cas.14134","volume":"110","author":"N Nishizawa","year":"2019","unstructured":"Nishizawa N, Harada H, Kumamoto Y, Kaizu T, Katoh H, Tajima H, et al. Diagnostic potential of hypermethylation of the cysteine dioxygenase 1 gene (CDO1) promoter DNA in pancreatic cancer. Cancer Sci. 2019;110:2846\u201355.","journal-title":"Cancer Sci"},{"key":"1674_CR10","doi-asserted-by":"publisher","first-page":"1644","DOI":"10.1111\/cas.14850","volume":"112","author":"H Harada","year":"2021","unstructured":"Harada H, Soeno T, Nishizawa N, Washio M, Sakuraya M, Ushiku H, et al. Prospective study to validate the clinical utility of DNA diagnosis of peritoneal fluid cytology test in gastric cancer. Cancer Sci. 2021;112:1644\u201354.","journal-title":"Cancer Sci"},{"key":"1674_CR11","doi-asserted-by":"publisher","first-page":"8604","DOI":"10.1021\/ac202028g","volume":"83","author":"BJ Hindson","year":"2011","unstructured":"Hindson BJ, Ness KD, Masquelier DA, Belgrader P, Heredia NJ, Makarewicz AJ, et al. High-throughput droplet digital PCR system for absolute quantitation of DNA copy number. Anal Chem. 2011;83:8604\u201310.","journal-title":"Anal Chem"},{"key":"1674_CR12","doi-asserted-by":"publisher","first-page":"9236","DOI":"10.1073\/pnas.96.16.9236","volume":"96","author":"B Vogelstein","year":"1999","unstructured":"Vogelstein B, Kinzler KW. Digital PCR. Proc Natl Acad Sci U S A. 1999;96:9236\u201341.","journal-title":"Proc Natl Acad Sci U S A"},{"key":"1674_CR13","doi-asserted-by":"publisher","first-page":"858","DOI":"10.1038\/nbt.1559","volume":"27","author":"M Li","year":"2009","unstructured":"Li M, Chen WD, Papadopoulos N, Goodman SN, Bjerregaard NC, Laurberg S, et al. Sensitive digital quantification of DNA methylation in clinical samples. Nat Biotechnol. 2009;27:858\u201363.","journal-title":"Nat Biotechnol"},{"key":"1674_CR14","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1373\/clinchem.2014.221366","volume":"61","author":"JF Huggett","year":"2015","unstructured":"Huggett JF, Cowen S, Foy CA. Considerations for digital PCR as an accurate molecular diagnostic tool. Clin Chem. 2015;61:79\u201388.","journal-title":"Clin Chem"},{"key":"1674_CR15","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2220704120","volume":"120","author":"Y Wang","year":"2023","unstructured":"Wang Y, Douville C, Cohen JD, Mattox A, Curtis S, Silliman N, et al. Detection of rare mutations, copy number alterations, and methylation in the same template DNA molecules. Proc Natl Acad Sci U S A. 2023;120:e2220704120.","journal-title":"Proc Natl Acad Sci U S A"},{"key":"1674_CR16","volume-title":"Japanese classification of gastric carcinoma","author":"JGC Association","year":"2017","unstructured":"Association JGC. Japanese classification of gastric carcinoma. 15th ed. Tokyo (Japan): Kanehara & Co., Ltd; 2017.","edition":"15"},{"key":"1674_CR17","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0113546","volume":"9","author":"K Yamashita","year":"2014","unstructured":"Yamashita K, Waraya M, Kim MS, Sidransky D, Katada N, Sato T, et al. Detection of methylated CDO1 in plasma of colorectal cancer; a PCR study. PLoS ONE. 2014;9:e113546.","journal-title":"PLoS ONE"},{"key":"1674_CR18","first-page":"1","volume":"30","author":"H Ushiku","year":"2017","unstructured":"Ushiku H, Yamashita K, Katoh H, Ema A, Minatani N, Kikuchi M, et al. Promoter DNA methylation of CDO1 gene and its clinical significance in esophageal squamous cell carcinoma. Dis Esophagus. 2017;30:1\u20139.","journal-title":"Dis Esophagus"},{"key":"1674_CR19","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.89173","volume":"12","author":"K Warnhoff","year":"2024","unstructured":"Warnhoff K, Bhattacharya S, Snoozy J, Breen PC, Ruvkun G. Hypoxia-inducible factor induces cysteine dioxygenase and promotes cysteine homeostasis in Caenorhabditis elegans. Elife. 2024;12:RP89173.","journal-title":"Elife"},{"key":"1674_CR20","doi-asserted-by":"publisher","first-page":"387","DOI":"10.1016\/j.ccr.2011.01.038","volume":"19","author":"T Ishimoto","year":"2011","unstructured":"Ishimoto T, Nagano O, Yae T, Tamada M, Motohara T, Oshima H, et al. CD44 variant regulates redox status in cancer cells by stabilizing the xCT subunit of system xc(-) and thereby promotes tumor growth. Cancer Cell. 2011;19:387\u2013400.","journal-title":"Cancer Cell"},{"key":"1674_CR21","doi-asserted-by":"publisher","first-page":"3695","DOI":"10.1111\/cas.13812","volume":"109","author":"K Yamashita","year":"2018","unstructured":"Yamashita K, Hosoda K, Nishizawa N, Katoh H, Watanabe M. Epigenetic biomarkers of promoter DNA methylation in the new era of cancer treatment. Cancer Sci. 2018;109:3695\u2013706.","journal-title":"Cancer Sci"},{"key":"1674_CR22","doi-asserted-by":"publisher","first-page":"4339","DOI":"10.1158\/1078-0432.CCR-19-2896","volume":"26","author":"B Liu","year":"2020","unstructured":"Liu B, Ricarte Filho J, Mallisetty A, Villani C, Kottorou A, Rodgers K, et al. Detection of promoter DNA methylation in urine and plasma aids the detection of non-small cell lung cancer. Clin Cancer Res. 2020;26:4339\u201348.","journal-title":"Clin Cancer Res"},{"key":"1674_CR23","doi-asserted-by":"publisher","first-page":"286","DOI":"10.1038\/nrg2005","volume":"8","author":"M Esteller","year":"2007","unstructured":"Esteller M. Cancer epigenomics: DNA methylomes and histone-modification maps. Nat Rev Genet. 2007;8:286\u201398.","journal-title":"Nat Rev Genet"},{"key":"1674_CR24","doi-asserted-by":"publisher","first-page":"336","DOI":"10.1007\/s10120-021-01252-y","volume":"25","author":"CD Zhang","year":"2022","unstructured":"Zhang CD, Takeshima H, Sekine S, Yamashita S, Liu YY, Hattori N, et al. Prediction of tissue origin of adenocarcinomas in the esophagogastric junction by DNA methylation. Gastric Cancer. 2022;25:336\u201345.","journal-title":"Gastric Cancer"}],"container-title":["Gastric Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10120-025-01674-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s10120-025-01674-y","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10120-025-01674-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T00:03:04Z","timestamp":1791849784000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s10120-025-01674-y"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,13]]},"references-count":24,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,1]]}},"alternative-id":["1674"],"URL":"https:\/\/doi.org\/10.1007\/s10120-025-01674-y","relation":{},"ISSN":["1436-3291","1436-3305"],"issn-type":[{"value":"1436-3291","type":"print"},{"value":"1436-3305","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,13]]},"assertion":[{"value":"28 June 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 September 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 October 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Takeshi Naitoh has financial relationships involving honoraria from Johnson & Johnson, Medtronic, Olympus, Sumitomo Bakelite, MC Medical, and Fujifilm for this study, as well as research grants from KAKENHI and honoraria from Taiho Pharmaceutical, Chugai Pharmaceutical, Daiichi Sankyo Co. Ltd., Eli Lilly Japan, and EA Pharma outside the submitted work. Koshi Kumagai has financial relationships involving honoraria from Abbott Japan LLC, The Japan Surgical Society, Medtronic Japan Co., Ltd., Miyarisan Pharmaceutical Co., Ltd., Nobelpharma Co., Ltd., Nutri Co., Ltd., Zeon Medical Inc., and Zeria Pharmaceutical Co., Ltd. outside the submitted work. Akira Ooki received speaker honoraria from Bristol Myers Squibb, Ono Pharmaceutical Co Ltd, Daiichi Sankyo, Astellas, and Taiho Pharmaceutical Co Ltd.","order":1,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"All procedures were approved by the Institutional Review Board of Kitasato University (approval no. B16-58), and conducted in accordance with the Declaration of Helsinki.","order":2,"name":"Ethics","label":"Ethics approval and consent to participate","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Informed consent or a substitute for it was obtained from all patients for inclusion in this study.","order":3,"name":"Ethics","label":"Consent for publication","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"This content has been made available to all.","name":"free","label":"Free to read"}]}}