Colon cancer subtypes: concordance, effect on survival and selection of the most representative preclinical models

Multiple gene-expression-based subtypes have been proposed for the molecular subdivision of colon cancer in the last decade. We aimed to cross-validate these classifiers to explore their concordance and their power to predict survival. A gene-chip-based database comprising 2,166 samples from 12 independent datasets was set up. A total of 22 different molecular subtypes were re-trained including the CCHS, CIN25, CMS, ColoGuideEx, ColoGuidePro, CRCassigner, MDA114, Meta163, ODXcolon, Oncodefender, TCA19, and V7RHS classifiers as well as subtypes established by Budinska, Chang, DeSousa, Marisa, Merlos, Popovici, Schetter, Yuen, and Watanabe (first authors). Correlation with survival was assessed by Cox proportional hazards regression for each classifier using relapse-free survival data. The highest efficacy at predicting survival in stage 2-3 patients was achieved by Yuen (p = 3.9e-05, HR = 2.9), Marisa (p = 2.6e-05, HR = 2.6) and Chang (p = 9e-09, HR = 2.35). Finally, 61 colon cancer cell lines from four independent studies were assigned to the closest molecular subtype.