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

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 stud...

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Autores principales: Chen, Fang, Li, Shenghui, Guo, Ruochun, Song, Fanghua, Zhang, Yue, Wang, Xifan, Huo, Xiaokui, Lv, Qingbo, Ullah, Hayan, Wang, Guangyang, Ma, Yufang, Yan, Qiulong, Ma, Xiaochi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10334131/
https://www.ncbi.nlm.nih.gov/pubmed/36198381
http://dx.doi.org/10.1016/j.jare.2022.09.012
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author Chen, Fang
Li, Shenghui
Guo, Ruochun
Song, Fanghua
Zhang, Yue
Wang, Xifan
Huo, Xiaokui
Lv, Qingbo
Ullah, Hayan
Wang, Guangyang
Ma, Yufang
Yan, Qiulong
Ma, Xiaochi
author_facet Chen, Fang
Li, Shenghui
Guo, Ruochun
Song, Fanghua
Zhang, Yue
Wang, Xifan
Huo, Xiaokui
Lv, Qingbo
Ullah, Hayan
Wang, Guangyang
Ma, Yufang
Yan, Qiulong
Ma, Xiaochi
author_sort Chen, Fang
collection PubMed
description 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-cohort area under the curve of 0.830 for discriminating colorectal cancer patients from controls. This model also showed consistently high accuracy in 2 independent validation cohorts (optimal area under the curve, 0.906). Gut virome analysis of adenoma patients identified 88 differential viruses and achieved an optimal area under the curve of 0.772 for discriminating patients from controls. CONCLUSION: Our findings demonstrate the gut virome characteristics in colorectal cancer and adenoma and highlight gut virus-bacterial synergy in the progression of colorectal cancer. The gut viral signatures may be new targets for colorectal cancer treatment. In addition, high repeatability and predictive power of the prediction models suggest the potential of gut viral biomarkers in non-invasive diagnostic tests of colorectal cancer and adenoma.
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spelling pubmed-103341312023-07-12 Meta-analysis of fecal viromes demonstrates high diagnostic potential of the gut viral signatures for colorectal cancer and adenoma risk assessment Chen, Fang Li, Shenghui Guo, Ruochun Song, Fanghua Zhang, Yue Wang, Xifan Huo, Xiaokui Lv, Qingbo Ullah, Hayan Wang, Guangyang Ma, Yufang Yan, Qiulong Ma, Xiaochi J Adv Res Original Article 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-cohort area under the curve of 0.830 for discriminating colorectal cancer patients from controls. This model also showed consistently high accuracy in 2 independent validation cohorts (optimal area under the curve, 0.906). Gut virome analysis of adenoma patients identified 88 differential viruses and achieved an optimal area under the curve of 0.772 for discriminating patients from controls. CONCLUSION: Our findings demonstrate the gut virome characteristics in colorectal cancer and adenoma and highlight gut virus-bacterial synergy in the progression of colorectal cancer. The gut viral signatures may be new targets for colorectal cancer treatment. In addition, high repeatability and predictive power of the prediction models suggest the potential of gut viral biomarkers in non-invasive diagnostic tests of colorectal cancer and adenoma. Elsevier 2022-10-02 /pmc/articles/PMC10334131/ /pubmed/36198381 http://dx.doi.org/10.1016/j.jare.2022.09.012 Text en © 2023 The Authors. Published by Elsevier B.V. on behalf of Cairo University. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Original Article
Chen, Fang
Li, Shenghui
Guo, Ruochun
Song, Fanghua
Zhang, Yue
Wang, Xifan
Huo, Xiaokui
Lv, Qingbo
Ullah, Hayan
Wang, Guangyang
Ma, Yufang
Yan, Qiulong
Ma, Xiaochi
Meta-analysis of fecal viromes demonstrates high diagnostic potential of the gut viral signatures for colorectal cancer and adenoma risk assessment
title Meta-analysis of fecal viromes demonstrates high diagnostic potential of the gut viral signatures for colorectal cancer and adenoma risk assessment
title_full Meta-analysis of fecal viromes demonstrates high diagnostic potential of the gut viral signatures for colorectal cancer and adenoma risk assessment
title_fullStr Meta-analysis of fecal viromes demonstrates high diagnostic potential of the gut viral signatures for colorectal cancer and adenoma risk assessment
title_full_unstemmed Meta-analysis of fecal viromes demonstrates high diagnostic potential of the gut viral signatures for colorectal cancer and adenoma risk assessment
title_short Meta-analysis of fecal viromes demonstrates high diagnostic potential of the gut viral signatures for colorectal cancer and adenoma risk assessment
title_sort meta-analysis of fecal viromes demonstrates high diagnostic potential of the gut viral signatures for colorectal cancer and adenoma risk assessment
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10334131/
https://www.ncbi.nlm.nih.gov/pubmed/36198381
http://dx.doi.org/10.1016/j.jare.2022.09.012
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