Allen Chi-Shing Yu, Jun Yu, Joseph Jao-Yiu Sung, Francis Ka Leung Chan, Paul Kay Sheung Chan, Matthew Tak Vai Chan, Siew Chien Ng, Martin Chi-Sang Wong, Zigui Chen, Xiansong Wang, Geicho Nakatsu, Thomas Yuen-Tung Lam, Naoki Sugimura, Chun-Ho Szeto, Xiangchun Li, Zhenwei Dai, Olabisi Oluwabukola Coker, Sunny Hei Wong, William Ka Kei Wu, Haokui Zhou
Journal: Gastroenterology 2018;155(2):529-541.e5
PMID: 29689266
Whilst research shows that patients with colorectal cancer (CRC) have a different microbiome composition to those without, little is known about differences in the virome, the collection of viruses in and on the human body. The authors investigated the viromes of faecal samples of patients with CRC and found that the gut virome differed between CRC patients and controls. Differences were also seen between early and late stage CRC patients, and certain virome profiles were associated with disease prognosis. The authors conclude that these virome “signatures” associated with CRC may be used for diagnostic purposes and to predict outcomes.
BACKGROUND & 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 the 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 forest 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 with controls. Twenty-two viral taxa discriminated cases from controls with an area under the receiver operating characteristic curve of 0.802 in the discovery cohort. The viral markers were validated in 3 cohorts, with area under the receiver operating characteristic curves of 0.763, 0.736, and 0.715, respectively. Clinical subgroup analysis showed that dysbiosis of the gut virome was 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) 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.
Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.
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