Meta-analysis of fecal viromes demonstrates high diagnostic potential of the gut viral signatures for colorectal cancer and adenoma risk assessment

作者：Fang Chen, Shenghui Li, Ruochun Guo, Fanghua Song, Yue Zhang, Xifan Wang, Xiaokui Huo, Qingbo Lv, Hayan Ullah, Guangyang Wang, Yufang Ma, Qiulong Yan, Xiaochi Ma · 发表于：Journal of Advanced Research · 年份：2022 · DOI：10.1016/j.jare.2022.09.012 · 被引用次数：52 · 研究领域：Bacteriophages and microbial interactions、Gut microbiota and health、Animal Virus Infections Studies

INTRODUCTION: Viruses have been reported as inducers of tumorigenesis. Little studies have explored the impact of the gut virome on the progression of colorectal cancer. However, there is still a problem with the repeatability of viral signatures across multiple cohorts. OBJECTIVES: The present study aimed to reveal the repeatable gut vial signatures of colorectal cancer and adenoma patients and decipher the potential of viral markers in disease risk assessment for diagnosis. METHODS: 1,282 available fecal metagenomes from 9 published studies for colorectal cancer and adenoma were collected. A gut viral catalog was constructed via a reference-independent approach. Viral signatures were identified by cross-cohort meta-analysis and used to build predictive models based on machine learning algorithms. New fecal samples were collected to validate the generalization of predictive models. RESULTS: The gut viral composition of colorectal cancer patients was drastically altered compared with healthy, as evidenced by changes in some Siphoviridae and Myoviridae viruses and enrichment of Microviridae, whereas the virome variation in adenoma patients was relatively low. Cross-cohort meta-analysis identified 405 differential viruses for colorectal cancer, including several phages of Porphyromonas, Fusobacterium, and Hungatella that were enriched in patients and some control-enriched Ruminococcaceae phages. In 9 discovery cohorts, the optimal risk assessment model obtained an average cross...