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

Autor:	Bramsen JB; Department of Molecular Medicine, Aarhus University Hospital, Aarhus 8200, Denmark. Electronic address: bramsen@clin.au.dk., Rasmussen MH; Department of Molecular Medicine, Aarhus University Hospital, Aarhus 8200, Denmark., Ongen H; Department of Genetic Medicine and Development, University of Geneva Medical School, Geneva 1211, Switzerland; Institute for Genetics and Genomics in Geneva (iGE3), University of Geneva, Geneva 1211, Switzerland; Swiss Institute of Bioinformatics, Geneva 1211, Switzerland., Mattesen TB; Department of Molecular Medicine, Aarhus University Hospital, Aarhus 8200, Denmark., Ørntoft MW; Department of Molecular Medicine, Aarhus University Hospital, Aarhus 8200, Denmark., Árnadóttir SS; Department of Molecular Medicine, Aarhus University Hospital, Aarhus 8200, Denmark., Sandoval J; Cancer Epigenetics and Biology Program, Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet, Barcelona 08908, Catalonia, Spain., Laguna T; Cancer Epigenetics and Biology Program, Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet, Barcelona 08908, Catalonia, Spain., Vang S; Department of Molecular Medicine, Aarhus University Hospital, Aarhus 8200, Denmark., Øster B; Department of Molecular Medicine, Aarhus University Hospital, Aarhus 8200, Denmark., Lamy P; Department of Molecular Medicine, Aarhus University Hospital, Aarhus 8200, Denmark., Madsen MR; Department of Surgery, Hospitalsenheden Vest, Herning 7400, Denmark., Laurberg S; Section of Coloproctology, Aarhus University Hospital, Aarhus 8000, Denmark., Esteller M; Cancer Epigenetics and Biology Program, Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet, Barcelona 08908, Catalonia, Spain; Physiological Sciences Department, School of Medicine and Health Sciences, University of Barcelona, Barcelona 08907, Catalonia, Spain; Institucio Catalana de Recerca i Estudis Avancats (ICREA), Barcelona 08010, Catalonia, Spain., Dermitzakis ET; Department of Genetic Medicine and Development, University of Geneva Medical School, Geneva 1211, Switzerland; Institute for Genetics and Genomics in Geneva (iGE3), University of Geneva, Geneva 1211, Switzerland; Swiss Institute of Bioinformatics, Geneva 1211, Switzerland., Ørntoft TF; Department of Molecular Medicine, Aarhus University Hospital, Aarhus 8200, Denmark., Andersen CL; Department of Molecular Medicine, Aarhus University Hospital, Aarhus 8200, Denmark. Electronic address: cla@clin.au.dk.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2017 May 09; Vol. 19 (6), pp. 1268-1280.
DOI:	10.1016/j.celrep.2017.04.045
Abstrakt:	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. (Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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