Gut Microbiota as Mediator and Moderator Between Hepatitis B Virus and Hepatocellular Carcinoma: A Prospective Study

ABSTRACT Background The impact of gut microbiome on hepatitis B virus (HBV)‐related hepatocellular carcinoma (HCC) is unclear. We aimed to evaluate the potential correlation between gut microbiome and HBV‐related HCC and introduced novel machine learning (ML) signatures based on gut microbe to predi...

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Main Authors: Bingren Hu, Yi Yang, Jiangqiao Yao, Ganglian Lin, Qikuan He, Zhiyuan Bo, Zhewei Zhang, Anlvna Li, Yi Wang, Gang Chen, Yunfeng Shan
Format: Article
Language:English
Published: Wiley 2024-12-01
Series:Cancer Medicine
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Online Access:https://doi.org/10.1002/cam4.70454
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author Bingren Hu
Yi Yang
Jiangqiao Yao
Ganglian Lin
Qikuan He
Zhiyuan Bo
Zhewei Zhang
Anlvna Li
Yi Wang
Gang Chen
Yunfeng Shan
author_facet Bingren Hu
Yi Yang
Jiangqiao Yao
Ganglian Lin
Qikuan He
Zhiyuan Bo
Zhewei Zhang
Anlvna Li
Yi Wang
Gang Chen
Yunfeng Shan
author_sort Bingren Hu
collection DOAJ
description ABSTRACT Background The impact of gut microbiome on hepatitis B virus (HBV)‐related hepatocellular carcinoma (HCC) is unclear. We aimed to evaluate the potential correlation between gut microbiome and HBV‐related HCC and introduced novel machine learning (ML) signatures based on gut microbe to predict the risk of HCC. Materials and Methods A total of 640 patients with chronic liver diseases or HCC were prospectively recruited between 2019 and 2022. Fecal samples were collected and subjected to 16S rRNA gene sequencing. Univariate and multivariate logistic regression was applied to identify risk characteristics. Several ML methods were employed to construct gut microbe‐based models and the predictive performance was evaluated. Results A total of 571 patients were involved in the study, including 374 patients with HCC and 197 patients with chronic liver diseases. After the propensity score matching method, 147 pairs of participants were enrolled in the analysis. Bacteroidia and Bacteroidales were demonstrated to exert mediating effects between HBV and HCC, and the moderating effects varied across Bacilli, Lactobacillales, Erysipelotrichaceae, Actinomyces, and Roseburia. HBV, alpha‐fetoprotein, alanine transaminase, triglyceride, and Child‐Pugh were identified as independent risk factors for HCC occurrence. Seven ML‐based HBV‐gut microbe models were established to predict HCC, with AUCs ranging from 0.821 to 0.898 in the training set and 0.813–0.885 in the validation set. Furthermore, the merged clinical‐HBV‐gut microbe models exhibited a comparable performance to HBV‐gut microbe models. Conclusions Gut microbes are important factors between HBV and HCC through its potential mediating and moderating effects, which can be used as valuable biomarkers for the pathogenesis of HBV‐related HCC.
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spelling doaj-art-426cb512c5554b90b5399b315a2ed53d2025-01-20T10:51:32ZengWileyCancer Medicine2045-76342024-12-011324n/an/a10.1002/cam4.70454Gut Microbiota as Mediator and Moderator Between Hepatitis B Virus and Hepatocellular Carcinoma: A Prospective StudyBingren Hu0Yi Yang1Jiangqiao Yao2Ganglian Lin3Qikuan He4Zhiyuan Bo5Zhewei Zhang6Anlvna Li7Yi Wang8Gang Chen9Yunfeng Shan10Department of Hepatobiliary and Pancreatic Surgery The First Affiliated Hospital of Wenzhou Medical University Wenzhou ChinaDepartment of Epidemiology and Biostatistics, School of Public Health Wenzhou Medical University Wenzhou ChinaDepartment of Hepatobiliary and Pancreatic Surgery The First Affiliated Hospital of Wenzhou Medical University Wenzhou ChinaDepartment of Hepatobiliary and Pancreatic Surgery The First Affiliated Hospital of Wenzhou Medical University Wenzhou ChinaDepartment of Hepatobiliary and Pancreatic Surgery The First Affiliated Hospital of Wenzhou Medical University Wenzhou ChinaDepartment of Hepatobiliary and Pancreatic Surgery The First Affiliated Hospital of Wenzhou Medical University Wenzhou ChinaThe First Clinical College Wenzhou Medical University Wenzhou ChinaThe First Clinical College Wenzhou Medical University Wenzhou ChinaDepartment of Epidemiology and Biostatistics, School of Public Health Wenzhou Medical University Wenzhou ChinaDepartment of Hepatobiliary and Pancreatic Surgery The First Affiliated Hospital of Wenzhou Medical University Wenzhou ChinaDepartment of Hepatobiliary and Pancreatic Surgery The First Affiliated Hospital of Wenzhou Medical University Wenzhou ChinaABSTRACT Background The impact of gut microbiome on hepatitis B virus (HBV)‐related hepatocellular carcinoma (HCC) is unclear. We aimed to evaluate the potential correlation between gut microbiome and HBV‐related HCC and introduced novel machine learning (ML) signatures based on gut microbe to predict the risk of HCC. Materials and Methods A total of 640 patients with chronic liver diseases or HCC were prospectively recruited between 2019 and 2022. Fecal samples were collected and subjected to 16S rRNA gene sequencing. Univariate and multivariate logistic regression was applied to identify risk characteristics. Several ML methods were employed to construct gut microbe‐based models and the predictive performance was evaluated. Results A total of 571 patients were involved in the study, including 374 patients with HCC and 197 patients with chronic liver diseases. After the propensity score matching method, 147 pairs of participants were enrolled in the analysis. Bacteroidia and Bacteroidales were demonstrated to exert mediating effects between HBV and HCC, and the moderating effects varied across Bacilli, Lactobacillales, Erysipelotrichaceae, Actinomyces, and Roseburia. HBV, alpha‐fetoprotein, alanine transaminase, triglyceride, and Child‐Pugh were identified as independent risk factors for HCC occurrence. Seven ML‐based HBV‐gut microbe models were established to predict HCC, with AUCs ranging from 0.821 to 0.898 in the training set and 0.813–0.885 in the validation set. Furthermore, the merged clinical‐HBV‐gut microbe models exhibited a comparable performance to HBV‐gut microbe models. Conclusions Gut microbes are important factors between HBV and HCC through its potential mediating and moderating effects, which can be used as valuable biomarkers for the pathogenesis of HBV‐related HCC.https://doi.org/10.1002/cam4.70454gut‐liver axisgut microbiotahepatitis B virushepatocellular carcinomamachine learning
spellingShingle Bingren Hu
Yi Yang
Jiangqiao Yao
Ganglian Lin
Qikuan He
Zhiyuan Bo
Zhewei Zhang
Anlvna Li
Yi Wang
Gang Chen
Yunfeng Shan
Gut Microbiota as Mediator and Moderator Between Hepatitis B Virus and Hepatocellular Carcinoma: A Prospective Study
Cancer Medicine
gut‐liver axis
gut microbiota
hepatitis B virus
hepatocellular carcinoma
machine learning
title Gut Microbiota as Mediator and Moderator Between Hepatitis B Virus and Hepatocellular Carcinoma: A Prospective Study
title_full Gut Microbiota as Mediator and Moderator Between Hepatitis B Virus and Hepatocellular Carcinoma: A Prospective Study
title_fullStr Gut Microbiota as Mediator and Moderator Between Hepatitis B Virus and Hepatocellular Carcinoma: A Prospective Study
title_full_unstemmed Gut Microbiota as Mediator and Moderator Between Hepatitis B Virus and Hepatocellular Carcinoma: A Prospective Study
title_short Gut Microbiota as Mediator and Moderator Between Hepatitis B Virus and Hepatocellular Carcinoma: A Prospective Study
title_sort gut microbiota as mediator and moderator between hepatitis b virus and hepatocellular carcinoma a prospective study
topic gut‐liver axis
gut microbiota
hepatitis B virus
hepatocellular carcinoma
machine learning
url https://doi.org/10.1002/cam4.70454
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