Abstract 3174: Colon cancer molecular subtypes: Concordance, effect on survival and selection of most representative preclinical models

Abstract

Abstract Introduction: Colon cancer is a genetically heterogeneous disease and there is an increasing need for more detailed classification of stage II and III patients. The NCCN guideline currently lists three FDA approved gene-expression based multi-gene prognostic tests for stage II-III colorectal cancer. However, it is undecided how many molecular subtype would most accurately describe these tumours. Here, we cross-validated known molecular subtypes for their concordance and capability to predict prognosis free survival. We utilized gene expression signatures to identify the most representative cell line model for each subtype. Materials and methods: Using publicly available datasets from the GEO repository we established a database containing clinical and microarray data for 2,166 colon cancer patients. Gene expression measured on Affymetrix HG-U133A and HG-U133 Plus2.0 arrays was processed according to authors’ description for each classifier in R. We conducted a systematic review of the literature in order to identify gene-expression based classifiers. We assigned each sample for these classificators and then compared their potential to predict recurrence free survival. Results: All together 22 different molecular subtypes were re-classified including the CCHS, CIN25, CMS, ColoGuideEx, ColoGuidePro, CRCassigner, MDA114, Meta163, ODXcolon, Oncodefender, TCA19, V7RHS classifiers as well as subtypes established by Budinska, Chang, DeSousa, Marisa, Merlos, Popovici, Schetter, Yuen, and Watanabe (first authors). When comparing the methods the most concordant classifiers were MDA114 and DeSousa (Cramer's V = 0.711). The highest efficacy to predict progression free survival in stage II-III 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). We also assigned 61 colon cancer cell lines from four independent studies to the closest molecular subtype. Conclusion: In summary, here we present a comprehensive analysis of human colon cancer molecular subtypes by cross-validation using independent transcriptomic datasets. Citation Format: Zsófia Sztupinszki, Balázs Győrffy. Colon cancer molecular subtypes: Concordance, effect on survival and selection of most representative preclinical models. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3174.