{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T11:03:45Z","timestamp":1791975825763,"version":"4.4.0"},"reference-count":52,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2021,10,30]],"date-time":"2021-10-30T00:00:00Z","timestamp":1635552000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Laboratory Analysis"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>In this study, we aimed to screen methylation signatures associated with the prognosis of patients with clear cell renal cell carcinoma (ccRCC).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Gene expression and methylation profiles of ccRCC patients were downloaded from publicly available databases, and differentially expressed genes (DEGs)\u2010differentially methylated genes (DMGs) were obtained. Subsequently, gene set enrichment and transcription factor (TF) regulatory network analyses were performed. In addition, a prognostic model was constructed and the relationship between disease progression and immunity was analyzed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A total of 23 common DEGs\u2010DMGs were analyzed, among which 14 DEGs\u2010DMGs were obtained with a cutoff value of PCC\u00a0&lt;\u00a00 and <jats:italic>p<\/jats:italic>\u00a0&lt;\u00a00.05. The enrichment analysis showed that the 14 DEGs\u2010DMGs were enriched in three GO terms and three KEGG pathways. In addition, a total of six TFs were shown to be associated with the 14 DEGs\u2010DMGs, including RP58, SOX9, NF\u2010\u03baB65, ATF6, OCT, and IK2. A prognostic model using five optimized DEGs\u2010DMGs which efficiently predicted survival was constructed and validated using the <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.ncbi.nlm.nih.gov\/geo\/query\/acc.cgi?acc=GSE105288\">GSE105288<\/jats:ext-link> dataset. Additionally, four types of immune cells (NK cells, macrophages, neutrophils, and cancer\u2010associated fibroblasts), as well as ESTIMATE, immune, and stromal scores were found to be significantly correlated with ccRCC progression (normal, primary, and metastasis) in addition to the five optimized DEGs\u2010DMGs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>A five\u2010gene methylation signature with the predictive ability for ccRCC prognosis was investigated in this study, consisting of <jats:italic>CCNB2<\/jats:italic>, <jats:italic>CDKN1C<\/jats:italic>, <jats:italic>CTSH<\/jats:italic>, <jats:italic>E2F2<\/jats:italic>, and <jats:italic>ERMP1<\/jats:italic>. In addition, potential targets for methylation\u2010mediated immunotherapy were highlighted.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcla.24031","type":"journal-article","created":{"date-parts":[[2021,10,30]],"date-time":"2021-10-30T07:41:49Z","timestamp":1635579709000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["A five\u2010gene methylation signature predicts overall survival of patients with clear cell renal cell carcinoma"],"prefix":"10.1002","volume":"35","author":[{"given":"Xiao","family":"Jing","sequence":"first","affiliation":[{"name":"Department of Urology The Second Affiliated Hospital of Zhejiang University School of Medicine Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gang","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Urology Shaoxing People's Hospital Shaoxing 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