biostudies-literatureRichards ARNCI NIH HHSNIHNIH HHS24https://www.ebi.ac.uk/biostudies/studies/S-EPMC12879400biostudies-literatureUnknown18(1)<h4>Background</h4>Protein EpiScores are a novel class of DNA methylation (DNAm)-based metrics proposed to measure peripheral immune system characteristics. Although Protein EpiScores have been associated with chronic disease risk, their relationship with colorectal cancer (CRC) survival has not been investigated.<h4>Methods</h4>We generated new genome-wide DNAm data on pre-treatment whole blood samples from a case-control sample of 136 newly diagnosed CRC patients nested in the ColoCare Study and calculated 107 Protein EpiScores using the developer's algorithm. Over a median follow-up of 7.3 years (range: 0.3-13.8 years), 35 (26%) patients experienced disease recurrence, and 47 (35%) died. Protein EpiScore associations with disease-free and overall survival were tested using Cox regressioClinical epigeneticsBlood DNA methylation-predicted plasma protein levels and colorectal cancer survival.PMC12879400P30-CA076292P30 CA076292Dowling BIToriola ATGigic BKresovich JKShibata DSiegel EMJean-Baptiste EGomez MFStewart PAFigueiredo JCLi CIRichards ARUlrich CMByrd DAfalseBlood DNA methylation-predicted plasma protein levels and colorectal cancer survival.<h4>Background</h4>Protein EpiScores are a novel class of DNA methylation (DNAm)-based metrics proposed to measure peripheral immune system characteristics. Although Protein EpiScores have been associated with chronic disease risk, their relationship with colorectal cancer (CRC) survival has not been investigated.<h4>Methods</h4>We generated new genome-wide DNAm data on pre-treatment whole blood samples from a case-control sample of 136 newly diagnosed CRC patients nested in the ColoCare Study and calculated 107 Protein EpiScores using the developer's algorithm. Over a median follow-up of 7.3 years (range: 0.3-13.8 years), 35 (26%) patients experienced disease recurrence, and 47 (35%) died. Protein EpiScore associations with disease-free and overall survival were tested using Cox regressio2026-01-01T00:00:00Z2026 Feb2026-07-15T13:17:21.172Z2026-07-05T03:08:20.328ZS-EPMC128794004162228910.1186/s13148-026-02059-3