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Metagenomic analysis of colorectal cancer datasets identifies cross-cohort microbial diagnostic signatures and a link with choline degradation
AM. Thomas, P. Manghi, F. Asnicar, E. Pasolli, F. Armanini, M. Zolfo, F. Beghini, S. Manara, N. Karcher, C. Pozzi, S. Gandini, D. Serrano, S. Tarallo, A. Francavilla, G. Gallo, M. Trompetto, G. Ferrero, S. Mizutani, H. Shiroma, S. Shiba, T....
Jazyk angličtina Země Spojené státy americké
Typ dokumentu časopisecké články, Research Support, N.I.H., Extramural, práce podpořená grantem
Grantová podpora
P30 CA042014
NCI NIH HHS - United States
R01 CA189184
NCI NIH HHS - United States
R01 CA207371
NCI NIH HHS - United States
NLK
ProQuest Central
od 2000-01-01 do Před 1 rokem
Health & Medicine (ProQuest)
od 2000-01-01 do Před 1 rokem
- MeSH
- cholin metabolismus MeSH
- databáze genetické MeSH
- druhová specificita MeSH
- kohortové studie MeSH
- kolorektální nádory diagnóza metabolismus mikrobiologie MeSH
- lidé MeSH
- lyasy genetika metabolismus MeSH
- metagenomika * MeSH
- nádorové biomarkery metabolismus MeSH
- střevní mikroflóra MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
Several studies have investigated links between the gut microbiome and colorectal cancer (CRC), but questions remain about the replicability of biomarkers across cohorts and populations. We performed a meta-analysis of five publicly available datasets and two new cohorts and validated the findings on two additional cohorts, considering in total 969 fecal metagenomes. Unlike microbiome shifts associated with gastrointestinal syndromes, the gut microbiome in CRC showed reproducibly higher richness than controls (P < 0.01), partially due to expansions of species typically derived from the oral cavity. Meta-analysis of the microbiome functional potential identified gluconeogenesis and the putrefaction and fermentation pathways as being associated with CRC, whereas the stachyose and starch degradation pathways were associated with controls. Predictive microbiome signatures for CRC trained on multiple datasets showed consistently high accuracy in datasets not considered for model training and independent validation cohorts (average area under the curve, 0.84). Pooled analysis of raw metagenomes showed that the choline trimethylamine-lyase gene was overabundant in CRC (P = 0.001), identifying a relationship between microbiome choline metabolism and CRC. The combined analysis of heterogeneous CRC cohorts thus identified reproducible microbiome biomarkers and accurate disease-predictive models that can form the basis for clinical prognostic tests and hypothesis-driven mechanistic studies.
Department CIBIO University of Trento Trento Italy
Department of Colorectal Surgery Clinica S Rita Vercelli Italy
Department of Computer Science University of Turin Turin Italy
Division of Cancer Genomics National Cancer Center Research Institute Tokyo Japan
European Institute of Oncology Milan Italy
Italian Institute for Genomic Medicine Turin Italy
Mucosal Immunology and Microbiota Unit Humanitas Research Hospital Milan Italy
School of Life Science and Technology Tokyo Institute of Technology Tokyo Japan
Structural and Computational Biology Unit European Molecular Biology Laboratory Heidelberg Germany
Citace poskytuje Crossref.org
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