Molecular-Subtype-Specific Biomarkers Improve Prediction of Prognosis in Colorectal Cancer

• DOI: 10.1016/j.celrep.2017.04.045
• Publication Date: 2017-05-09T19:01:06Z
• Authors: Jesper Bertram Br...; Mads Heilskov Ras...; Halit Ongen; Trine Block Mattesen; Mai-Britt Worm Ør...; Sigrid Salling Ár...; Juan Sandoval; Teresa Laguna; Søren Vang; Bodil Øster; Philippe Lamy; Mogens Rørbæk Madsen; Søren Laurberg; Manel Esteller; Emmanouil Theophi...; Torben Falck Ørntoft; Claus Lindbjerg A...
• Keywords: 0301 basic medicine; Cancer cells; Pronòstic mèdic; QH301-705.5; microbiome; colorectal cancer; archetype; molecular subtyping; 03 medical and health sciences; Càncer colorectal; Journal Article; Biomarkers, Tumor; Tumor Microenvironment; tumor microenvironment; Humans; ddc:576.5; prognostification; Biology (General); prognostic biomarker; molecular subtypes; CMS; info:eu-repo/classification/ddc/576.5; Microbiota; Biochemical markers; Prognosis; CRC classification; Colorectal cancer; CRC; 3. Good health; Case-Control Studies; Marcadors bioquímics; Cèl·lules canceroses; Colorectal Neoplasms; Transcriptome

Colorectal cancer (CRC) is characterized by major inter-tumor diversity that complicates the prediction of disease and treatment outcomes. Recent efforts help resolve this by sub-classification of CRC into natural molecular subtypes; however, this strategy is not yet able to provide clinicians with improved tools for decision making. We here present an extended framework for CRC stratification that specifically aims to improve patient prognostication. Using transcriptional profiles from 1,100 CRCs, including >300 previously unpublished samples, we identify cancer cell and tumor archetypes and suggest the tumor microenvironment as a major prognostic determinant that can be influenced by the microbiome. Notably, our subtyping strategy allowed identification of archetype-specific prognostic biomarkers that provided information beyond and independent of UICC-TNM staging, MSI status, and consensus molecular subtyping. The results illustrate that our extended subtyping framework, combining subtyping and subtype-specific biomarkers, could contribute to improved patient prognostication and may form a strong basis for future studies.