ORIGINAL RESEARCH article
Front. Microbiol.
Sec. Microorganisms in Vertebrate Digestive Systems
Volume 16 - 2025 | doi: 10.3389/fmicb.2025.1653249
This article is part of the Research TopicUnlocking the Potential of the Microbiome in Cancer TherapyView all articles
Integrated microbiome-metabolome profiling unveils a predictive signature for early recurrence in hepatocellular carcinoma
Provisionally accepted
- Department of Pathology, Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, China
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Hepatocellular carcinoma (HCC) exhibits high recurrence rates post-resection, yet predictive biomarkers remain elusive. Emerging evidence implicates intratumoral microbiota in cancer progression, but its role in HCC recurrence is unexplored. Here, we characterized microbial and metabolic profiles in 90 HCC patients (49 with early recurrence [RFS ≤2 years], 41 non-recurrent controls) using 16S rRNA sequencing and LC-MS metabolomics. Recurrent tumors showed reduced microbial diversity (Shannon index, P<0.05) and distinct compositional shifts, including enrichment of Proteobacteria (LEfSe LDA>4) and depletion of commensals like Akkermansia. A 20microbial-genus signature predicted recurrence (AUC=0.81, 95% CI:0.72-0.91), while a 20-metabolite panel (e.g., resolvin D5, γ-glutamylthreonine) achieved superior accuracy (AUC=0.958, CI:0.950-0.966). Functional analyses linked recurrence-associated microbiota with disrupted lipid/amino acid metabolism and proinflammatory pathways (KEGG, P<0.01). Microbial-metabolite correlation networks revealed strong associations between dysbiotic taxa (e.g., Cyanobacteria) and immunomodulatory metabolites (*r*>0.6, P<0.05). This study identifies intra-tumoral microbiome-metabolome signatures as novel biomarkers for HCC recurrence, offering mechanistic insights into microbial regulation of the tumor microenvironment and clinical tools for post-surgical risk stratification.
Keywords: hepatocellular carcinoma (HCC), intra-tumoral microbiome, early recurrence, diagnostic micro-biomarkers, Microbial metabolomics
Received: 24 Jun 2025; Accepted: 13 Aug 2025.
Copyright: © 2025 Qu, Chen, Wang, Wu, Zhang and Xia. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Dingding Qu, Department of Pathology, Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, China
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