ArticleCancer discovery2025
Intrahepatic Microbial Heterogeneity in Multifocal Hepatocellular Carcinoma and Its Association with Host Genomic and Transcriptomic Alterations.
Article in Cancer discovery, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed.
- Characterization of the intrahepatic microbiome in patients with HBV-related end-stage liver disease.Virulence · 2026Article
- Beyond probiotics and pathobionts: mechanistic roles of enterococcus-derived bioactive components in health and disease.Folia microbiologica · 2026Review
- Heterogeneity in cancer: molecular mechanisms and therapeutic strategies.Signal transduction and targeted therapy · 2026Review
- Microbiota in the Tumor Metastatic Cascade: Emerging Evidence Across Invasion, Circulation, and Colonization.International journal of molecular sciences · 2026Review
- Review
- Cancer Heterogeneity and Cancer Cell Plasticity: Molecular Mechanisms and Precision Therapy.MedComm · 2026Review
- Spatial Heterogeneity of Intratumoral Microbiota and Its Roles in Tumor-Microbiota Interactions and Therapeutic Implications.Pathogens (Basel, Switzerland) · 2026Review
- Hepatocellular carcinoma metastasis-immune microenvironment crosstalk: emerging mechanisms and immunotherapy.Cellular & molecular biology letters · 2026Review
- A tumor-residentiScience · 2026Article
- Intratumoral microbiota in cancer: molecular mechanism and therapeutic strategies.Molecular biomedicine · 2026Review
- Tumor-resident bacteria in gastrointestinal cancers: from regulatory mechanisms to clinical implications.Cancer biology & medicine · 2026Review
- How the gut microbiome affects the immunotherapy response in hepatocellular carcinoma.Cancer biology & medicine · 2026Review
- Immunosuppressive Microenvironment Reprogramming by Synergistic Sonodynamic Therapy of Phthalocyanine-MOF Hybrids for Hepatocellular Carcinoma.Exploration (Beijing, China) · 2026Article
- Global Advances in Hepatocellular Carcinoma Research and Therapy in 2025.Cancer innovation · 2026Review
- Multi-omics profiling reveals divergent biology and liver microenvironment in HCC of metastatic and de novo origin.Molecular cancer · 2026Article
- The "Cold Tumor" to "Hot Tumor" transformation strategy for triple-negative breast cancer: from mechanism to clinical translation.Molecular and cellular biochemistry · 2026Review
- IntratumoralScience advances · 2026Article
- Enterococcus faecalis-induced bystander effect causes epigenetic alterations leading to aberrant TGF-β signaling and epithelial-mesenchymal transition.Cell communication and signaling : CCS · 2026Article
- Functional Interpretation of Recurrent Genetic Variants in Hepatocellular Carcinoma: Molecular Consequences and Clinical Relevance.Human mutation · 2026Review
- The landscape of gut microbiota in hepatocarcinogenesis: a comprehensive review of pathogenesis and therapeutic interventions.International journal of surgery (London, England) · 2026Review
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Authors and funding
18 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The signature of the intrahepatic microbiome in multifocal hepatocellular carcinoma (HCC) and its association with genomic alterations remain elusive. In this study, we performed multiomics profiling of 242 HCC tumor nodules and 58 adjacent nontumor tissues from 58 patients with multifocal HCC, revealing heterogeneous microbial communities in multifocal HCC. The presence of bacteria in HCC nodules was confirmed by Gram stain, lipopolysaccharide, lipoteichoic acid staining, and transmission electron microscopy. Mutational profiling stratified patients into intrahepatic metastasis (IM)-HCC and multicentric occurrence (MO)-HCC. Bacterial communities differed between IM and MO nodules (P = 0.01). A nine-bacterium biomarker panel could distinguish IM nodules from MO nodules with an AUROC of 0.795. The epithelial-mesenchymal transition pathway was upregulated in IM nodules and correlated with IM-enriched bacteria. IM-enriched bacteria such as Enterococcus faecalis and Streptococcus anginosus promoted HCC cell migration, invasion, and tumor progression in orthotopic HCC mouse models by inducing an immunosuppressive microenvironment and epithelial-mesenchymal transition. Collectively, the intrahepatic microbiome contributes to the heterogeneity and pathogenesis of multifocal HCC. SIGNIFICANCE: We reveal intraindividual heterogeneous microbial communities among nodules from patients with multifocal HCC. IM-HCC-enriched bacteria promote tumor growth and influence the tumor microenvironment of HCC. Our work highlights the necessity of considering bacterial heterogeneity as biomarkers and targets for multifocal HCC therapeutic intervention. See related commentary by Dzutsev and Trinchieri, p. 1540.
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