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

Cell Reports
Jesper Bertram BramsenClaus Lindbjerg Andersen

Abstract

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300 previously unpublished samples, we identify cancer cell and tumor archetypes and suggest the tumor microenvironment as a major prognostic determinant that can be influenced by the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.

Citations

Jan 10, 2018·Proteomics·Lay Cheng Lim, Yang Mooi Lim
Jan 24, 2018·World Journal of Gastroenterology : WJG·Zhen-Qiang SunWei-Tang Yuan
Jul 11, 2019·Nature Reviews. Clinical Oncology·Anita SveenRagnhild A Lothe
Feb 1, 2019·Current Gastroenterology Reports·David G MenterScott Kopetz
Sep 25, 2020·Clinics in Colon and Rectal Surgery·Jyotsna BhudiaMarcia Hall
Sep 10, 2020·Current Colorectal Cancer Reports·Anup KasiWeijing Sun
Nov 28, 2019·Cell Death & Disease·Sara SteinmannRegine Schneider-Stock
Nov 28, 2018·International Journal of Molecular Sciences·Chiara MolinariPaola Ulivi
Jun 13, 2021·Archives of Biochemistry and Biophysics·Shanping ShiYang Xi
Jun 3, 2021·Journal of the National Cancer Institute·Sanne Ten HoornLouis Vermeulen

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