Identification of intratumoral bacteria correlated with hepatitis B virus (HBV) levels: a prognostic indicator for patient outcomes in hepatocellular carcinoma patients

ABSTRACT Hepatocellular carcinoma (HCC) is a prevalent liver cancer associated with global health. The tumor microenvironment’s (TME) microbial composition significantly influences HCC’s development and prognosis. This study analyzed bacterial 16S rRNA genes from liver cancer patients’ tumor, adjacent tumor, and normal tissues, revealing distinct microbiome profiles between tumor and normal tissues. HCC microbiota was more abundant, with Bacteroides , Ochrobactrum , Akkermansia , and Lactobacillus as the most prevalent genera. Hepatitis B virus (HBV)-positive (HBV+) and HBV-negative (HBV−) HCC tissues showed different microbial network patterns, with Bacteroides enrichment in HBV+ tissues being associated with HCC prognosis. HBV is associated with clinicopathological features and serves as an independent prognostic factor in HCC. The study underscores the microbiota’s complexity in HCC and the potential of HBV as a prognostic biomarker post-surgery. This study provides critical insights into the relationship between the microbiota within the TME and HCC, a leading cause of cancer-related mortality. By identifying distinct microbiome profiles in HCC patients, particularly the enrichment of Bacteroides in HBV-positive tissues, our research not only uncovers the complexity of microbial interactions in liver cancer but also highlights the potential of using HBV status as a prognostic biomarker. This could significantly inform personalized treatment strategies and improve clinical outcomes for HCC patients, emphasizing the relevance of microbiome-based diagnostics and therapies in oncology. IMPORTANCE In our study of the tumor microenvironment (TME) in hepatocellular carcinoma (HCC), we used DNA sequencing of bacterial 16S rRNA genes to analyze microbial compositions in tumor, adjacent tumor, and normal tissues from 213 liver cancer patients. Fluorescence in situ hybridization confirmed the presence of microbiota within tumors. Our results showed significant differences in microbiome profiles between tumor and normal tissues, with increased abundance of Bacteroides , Ochrobactrum , Akkermansia , and Lactobacillus in the HCC TME. Hepatitis B virus (HBV) status further stratified these differences, with Bacteroides significantly enriched in HBV-positive tissues and correlating with patient prognosis. Additionally, Bacteroides and Akkermansia showed interdependent population changes. Clinicopathological features, such as tumor size, were associated with HBV status, identifying HBV infection as an independent prognostic factor. These findings highlight the HCC microbiota’s complexity and suggest HBV status as a potential prognostic biomarker, opening avenues for personalized therapeutic strategies.