Potential of fecal microbiota for early‐stage detection of colorectal cancer

Molecular Systems Biology - Tập 10 Số 11 - 2014
Georg Zeller1, Julien Tap2,1, Anita Y. Voigt3,4,5,1, Shinichi Sunagawa1, Jens Roat Kultima1, Paul Igor Costea1, Aurélien Amiot2, Jürgen Böhm6,7, Francesco Brunetti8, Nina Habermann6,7, Rajna Hercog9, Moritz Koch10, Alain Luciani11, Daniel R. Mende1, Martin Schneider10, Petra Schrotz‐King6,7, Christophe Tournigand12, Jeanne Tran Van Nhieu13, Takuji Yamada14, Jürgen Zimmermann9, Vladimı́r Beneš9, Matthias Kloor3,4,5, Cornelia M. Ulrich6,15,15, Magnus von Knebel Doeberitz3,4,5, Iradj Sobhani2, Peer Bork16,5
1Structural and Computational Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany
2Department of Gastroenterology and LIC‐EA4393‐EC2M3 APHP and UPEC Université Paris‐Est Créteil Créteil France
3Clinical Cooperation Unit Applied Tumor Biology, German Cancer Research Center (DKFZ), Heidelberg, Germany
4Department of Applied Tumor Biology, Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany
5Molecular Medicine Partnership Unit (MMPU) University Hospital Heidelberg and European Molecular Biology Laboratory Heidelberg Germany
6Division of Preventive Oncology National Center for Tumor Diseases (NCT) Heidelberg Heidelberg Germany
7German cancer Research Center (DKFZ), Heidelberg, Germany
8Department of Surgery APHP and UPEC Université Paris‐Est Créteil Créteil France
9Genomics Core Facility, European Molecular Biology Laboratory, Heidelberg, Germany
10Department of General, Visceral and Transplantation Surgery, University Hospital Heidelberg, Heidelberg, Germany
11Department of Radiology APHP and UPEC Université Paris‐Est Créteil Créteil France
12Department of Medical Oncology APHP and UPEC Université Paris‐Est Créteil Créteil France
13Department of Pathology and LIC‐EA4393‐EC2M3 APHP and UPEC Université Paris‐Est Créteil Créteil France
14Department of Biological Information, Tokyo Institute of Technology, Tokyo, Japan
15Fred Hutchinson Cancer Research Center (FHCRC), Seattle, WA, USA
16Max Delbrück Centre for Molecular Medicine, Berlin, Germany

Tóm tắt

AbstractSeveral bacterial species have been implicated in the development of colorectal carcinoma (CRC), butCRC‐associated changes of fecal microbiota and their potential for cancer screening remain to be explored. Here, we used metagenomic sequencing of fecal samples to identify taxonomic markers that distinguishedCRCpatients from tumor‐free controls in a study population of 156 participants. Accuracy of metagenomicCRCdetection was similar to the standard fecal occult blood test (FOBT) and when both approaches were combined, sensitivity improved > 45% relative to theFOBT, while maintaining its specificity. Accuracy of metagenomicCRCdetection did not differ significantly between early‐ and late‐stage cancer and could be validated in independent patient and control populations (N = 335) from different countries.CRC‐associated changes in the fecal microbiome at least partially reflected microbial community composition at the tumor itself, indicating that observed gene pool differences may reveal tumor‐related host–microbe interactions. Indeed, we deduced a metabolic shift from fiber degradation in controls to utilization of host carbohydrates and amino acids inCRCpatients, accompanied by an increase of lipopolysaccharide metabolism.

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Molecular Systems Biology

Tập 10 Số 11

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