Intratumoral microbiome evaluated progression and outcome of patients with HBV-associated hepatocellular carcinoma.

BACKGROUND: Infection of hepatitis B virus (HBV) is a well-known risk factor for hepatocellular carcinoma (HCC). It is currently unknown whether gut microbiome dysbiosis in HCC tissue affects the assessment of progression and clinical outcome in patients with HBV-associated HCC. METHODS: Through a comparative analysis of 16 S gene fragments and biomarkers in tumor tissues from 40 HBV-associated HCC patients, we gained novel insights into the microbiome characteristics of HBV-associated HCC patients. RESULTS: LEfSe analysis indicated that Burkholderia cepacia (s), Microcuccus luteus (s) and Microcuccus (g) were dominant in HBV-associated HCC tissues (p < 0.05). 16 S rRNA-positive bacteria were not only localized in HCC cells but also overlapped with some of cells with CD68-, MPO-, α-SMA-, or CD34- positive staining in the tumor tissues. We observed that taxa abundance in HCC tissues was significantly associated with clinicopathological variables, such as tumor size, differentiation, invasion of the liver capsule, lymphovascular invasion, metastasis, pTNM, portal hypertension (PTH), Child-Turcotte-Pugh score, BCLC stage, prognosis (overall survival and progression-free survival), serum levels of α-fetoprotein, albumin, and glucose and personal habits (such as smoking and alcohol intake) of the HBV-associated HCC patients (p < 0.05). CONCLUSIONS: This study demonstrated that microbiome dysbiosis would have a profound effect on the progression and outcome of HBV-associated HCC. B. cepacia (s), M. luteus (s), and Microcuccus (g) would be taxon signatures in HBV-associated HCC tissues and might serve as potential targets for the treatment of patients with HBV-associated HCC.