Molecular subtyping improves prognostication of Stage 2 colorectal cancer

Abstract

Background: Post-surgical staging is the mainstay of prognostic stratification for colorectal cancer (CRC). Here, we compare TNM staging to consensus molecular subtyping (CMS) and assess the value of subtyping in addition to stratification by TNM. Methods: Three hundred and eight treatment-naïve colorectal tumours were accessed from our institutional tissue bank. CMS typing was carried out using tumour gene-expression data. Post-surgical TNM-staging and CMS were analysed with respect to clinicopathologic variables and patient outcome. Results: CMS alone was not associated with survival, while TNM stage significantly explained mortality. Addition of CMS to TNM-stratified tumours showed a prognostic effect in stage 2 tumours; CMS3 tumours had a significantly lower overall survival (P = 0.006). Stage 2 patients with a good prognosis showed immune activation and up-regulation of tumour suppressor genes. Conclusions: Although stratification using CMS does not outperform TNM staging as a prognostic indicator, gene-expression based subtyping shows promise for improved prognostication in stage 2 CRC.