HCV- and HBV-mediated liver cancer converge on similar transcriptomic landscapes and immune profiles.

ABSTRACT

Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related deaths worldwide, and a large proportion of HCC is attributable to viral causes including hepatitis B (HBV) and C virus (HCV). The pathogenesis of viral-mediated HCC can differ between HBV and HCV, but it is unclear how much these differences influence the tumors' final molecular and immune profiles. Additionally, there are known sex differences in the molecular etiology of HCC, but sex differences have not been explored in the context of viral-mediated HCC. To determine the extent to which the viral status and sex impact the molecular and immune profiles of HCC, we performed differential expression and immune cell deconvolution analyses. We identified a large number of differentially expressed genes unique to the HBV or HCV tumortumor-adjacent comparison. Pathway enrichment analyses demonstrated that the changes unique to the HCV tumortumor-adjacent tissue were predominated by changes in the immune pathways. Immune cell deconvolution demonstrated that HCV tumor-adjacent tissue had the largest immune cell infiltrate, with no difference in the immune profiles within HBV and HCV tumor samples. We subsequently segregated the differential expression analyses by sex, but demonstrated that the low number of female samples led to an overestimate of differentially expressed genes unique to male tumors. This limitation highlights the importance of additional sampling of female HCC tumors to allow for a more complete analysis of the sex differences in HCC. Overall, this work demonstrates the convergence of HBV- and HCV-mediated HCC on a similar transcriptomic landscape and immune profile despite differences in the surrounding tissue.