Alterations in Enteric Virome Are Associated With Colorectal Cancer and Survival Outcomes
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AbstractBackground and aims
Patients with colorectal cancer (CRC) have a different gut microbiome signature than individuals without CRC. Little is known about the viral component of CRC-associated microbiome. We aimed to identify and validate viral taxonomic markers of CRC that might be used in detection of disease or predicting outcome.

Methods
We performed shotgun metagenomic analyses of viromes of fecal samples from 74 patients with CRC (cases) and 92 individuals without CRC (controls) in Hong Kong (discovery cohort). Viral sequences were classified by taxonomic alignment against an integrated microbial reference genome database. Viral markers associated with CRC were validated using fecal samples from 3 separate cohorts: 111 patients with CRC and 112 controls in Hong Kong, 46 patients with CRC and 63 controls in Austria, and 91 patients with CRC and 66 controls in France and Germany. Using abundance profiles of CRC-associated virome genera, we constructed random survival forests models to identify those associated with patient survival times.

Results
The diversity of the gut bacteriophage community was significantly increased in patients with CRC compared to controls. Twenty-two viral taxa discriminated cases from controls with an area under the receiver operating characteristic curve (AUROC) of 0.802 in the discovery cohort. The viral markers were validated in 3 cohorts, with AUROCs of 0.763, 0.736, and 0.715. Clinical subgroup analysis showed that dysbiosis of the gut virome associated with early- and late-stage CRC. A combination of 4 taxonomic markers associated with reduced survival of patients with CRC (log-rank test, P=8.1 × 10-6) independently of tumor stage, lymph node metastases, or clinical parameters. We found altered interactions between bacteriophages and oral bacterial commensals in fecal samples from patients with CRC compared with controls.

Conclusions
In a metagenomic analysis of fecal samples from patients and controls, we identified virome signatures associated with CRC. These data might be used to develop tools to identify individuals with CRC or predict outcomes.
Acceptance Date17/04/2018
All Author(s) ListNakatsu G, Zhou HK, Wu WKK, Wong SH, Coker OO, Dai ZW, Li XC, Szeto CH, Sugimura N, Lam TYT, Yu ACS, Wang XS, Chen ZG, Wong MCS, Ng SC, Chan MTV, Chan PKS, Chan FKL, Sung JJY, Yu J
Journal nameGastroenterology
Year2018
Month8
Volume Number155
Issue Number2
Pages529 - 541.e5
ISSN0016-5085
eISSN1528-0012
LanguagesEnglish-United Kingdom
Keywordsmicrobiome, stool, sequencing, colorectal cancer

Last updated on 2020-24-05 at 01:36