{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T18:48:43Z","timestamp":1792867723527,"version":"4.5.0"},"reference-count":51,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2022,10,11]],"date-time":"2022-10-11T00:00:00Z","timestamp":1665446400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Natural Science Foundation of China","award":["82102183"],"award-info":[{"award-number":["82102183"]}]},{"name":"National Natural Science Foundation of China","award":["82103261"],"award-info":[{"award-number":["82103261"]}]},{"name":"National Natural Science Foundation of China","award":["81501965"],"award-info":[{"award-number":["81501965"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background: Immunotherapy is recently being used to treat esophageal squamous cell carcinoma (ESCC); however, response and survival benefits are limited to a subset of patients. A better understanding of the molecular heterogeneity and tumor immune microenvironment in ESCC is needed for improving disease management. Methods: Based on the DNA methylation and gene expression profiles of ESCC patients, we identify molecular subtypes of patients and construct a predictive model for subtype classification. The clinical value of molecular subtypes for the prediction of immunotherapy efficacy is assessed in an independent validation cohort of Chinese ESCC patients who receive immunotherapy. Results: We identify two molecular subtypes of ESCC (S1 and S2) that are associated with distinct immune-related pathways, tumor microenvironment and clinical outcomes. Accordingly, S2 subtype patients had a poorer prognosis. A 15-gene expression signature is developed to classify molecular subtypes with an overall accuracy of 94.7% (89\/94, 95% CI: 0.880\u20130.983). The response rate of immunotherapy is significantly higher in the S1 subtype than in the S2 subtype patients (68.75% vs. 25%, p = 0.028). Finally, potential target drugs, including mitoxantrone, are identified for treating patients of the S2 subtype. Conclusions: Our findings demonstrated that the identified molecular subtypes constitute a promising prognostic and predictive biomarker to guide the clinical care of ESCC patients.<\/jats:p>","DOI":"10.3390\/cancers14204970","type":"journal-article","created":{"date-parts":[[2022,10,11]],"date-time":"2022-10-11T06:13:27Z","timestamp":1665468807000},"page":"4970","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Genome-Wide DNA Methylation and Gene Expression Profiling Characterizes Molecular Subtypes of Esophagus Squamous Cell Carcinoma for Predicting Patient Survival and Immunotherapy Efficacy"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4035-3690","authenticated-orcid":false,"given":"Yulong","family":"Zheng","sequence":"first","affiliation":[{"name":"Department of Medical Oncology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiqi","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Pathology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingyun","family":"Su","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng","family":"Xiao","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Thoracic Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, China"},{"name":"Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shenglin","family":"Huang","sequence":"additional","affiliation":[{"name":"The Shanghai Key Laboratory of Medical Epigenetics, Fudan University Shanghai Cancer Center, Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0957-0547","authenticated-orcid":false,"given":"Yifeng","family":"Sun","sequence":"additional","affiliation":[{"name":"The Canhelp Genomics Research Center, Canhelp Genomics Co., Ltd., Hangzhou 311199, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheng","family":"Wu","sequence":"additional","affiliation":[{"name":"The Canhelp Genomics Research Center, Canhelp Genomics Co., Ltd., Hangzhou 311199, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yixin","family":"Wo","sequence":"additional","affiliation":[{"name":"The Canhelp Genomics Research Center, Canhelp Genomics Co., Ltd., Hangzhou 311199, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qinghua","family":"Xu","sequence":"additional","affiliation":[{"name":"The Canhelp Genomics Research Center, Canhelp Genomics Co., Ltd., Hangzhou 311199, China"},{"name":"The Institute of Machine Learning and Systems Biology, College of Electronics and Information Engineering, Tongji University, Shanghai 201804, China"},{"name":"Xuzhou Engineering Research Center of Medical Genetics and Transformation, Department of Genetics, Xuzhou Medical University, Xuzhou 221004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nong","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Thoracic Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, China"},{"name":"Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"209","DOI":"10.3322\/caac.21660","article-title":"Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA A Cancer J. 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