Specific gut microbiome signature predicts hepatitis B virus-related hepatocellular carcinoma patients with microvascular invasion

Abstract

Abstract Background Microvascular Invasion (MVI) is an important factor that affects the prognosis of patients with operable hepatocellular carcinoma. We aimed to evaluate the differences in intestinal microflora between MVI and non-MVI patients with operable hepatitis B virus-related hepatocellular carcinoma (HBV-HCC) and investigate the potential of the microbiome as a non-invasive biomarker for patients with MVI.Methods The preoperative relationship between the gut microbiomes (GM) of the two groups(MVI Group (n = 46) and non-MVI Group (n = 56)) was assessed using 16S ribosomal RNA gene sequencing data. PICRUST2 was used to analyze the metagenomic data in MVI and non-MVI patients. based on operational taxonomic units (OTUs) level, we predict MVI risk using random forest (RF)models, and validate in independent validation cohorts (MVI Group (n = 17) and non-MVI Group (n = 15)).Result β diversity analysis revealed a significant difference between the MVI group and non-MVI group in weighted UniFrac distances using Non-metric multidimensional scaling (stress = 0.105)and Principal Coordinates Analysis ( AMOVA test (p = 0.003)). At the genus level, eight bacterial genera (Prevotella_9, Bacteroides, Subdoligranulum, Fusobacterium, Dialister, Megasphaera, Veillonella, Coprobacter) were significantly enriched in MVI Group, whereas ten genera (Blautia, Faecalibacterium, Agathobacter, Ruminococcus, Erysipelotrichaceae_UCG-003, Anaerostipes, [Eubacterium]_hallii_group, Fusicatenibacter, Dorea, Peptoniphilus) were significantly enriched in non-MVI Group. The highly abundant genera participated in numerous amino acid metabolism pathways, pyrimidine and purine metabolism pathways, tetrahydrofolate metabolism pathways, fatty acid related metabolic pathway, glycogen degradation pathway, rhamnose, galactose, peptidoglycan metabolism pathways and lactate relative pathway. A significant correlation was observed between the characteristic intestinal microbial community and its main functions. Nine optimal microbial markers were determined, with an area under the curve of 79.76% between 46 MVI and 56 non-MVI samples and 79.80% in the independent verification group.Conclusion The characteristics of the intestinal microflora of patients with and non-MVI were analyzed for the first time, which may eventually help open up a new approach for the treatment of HBV-HCC with MVI. The successful establishment of a diagnostic model and independent verification of microbial markers in patients with MVI was reported. GM as a preoperative targeted biomarkers may be potential non-invasive tools for patients with HBV-HCC with MVI.