ZNF385A and ZNF346 Serve as Prognostic Biomarkers Associated with an Inflamed Immunosuppressive Tumor Microenvironment in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) has a high mortality rate worldwide, and there are still many problems in the early diagnosis, molecular targeted therapy, and immunotherapy. It is necessary to explore valuable diagnostic markers and new therapeutic targets in HCC. Zinc finger protein 385A () and zinc finger protein 346 () represent a unique class of RNA-binding Cys2 His2 (C2H2) zinc finger proteins that are involved in the regulation of cell cycle and apoptosis, but little is known of their roles in HCC. Based on multiple databases and analysis tools, we explored the expression, clinical relation, prognostic value, possible biological function, and pathways of and , and their relationship with immune infiltration. Our results revealed that and were highly expressed and were associated with poor prognosis in HCC. Hepatitis B virus (HBV) infection may lead to the overexpression of and , which was accompanied by elevated apoptosis and chronic inflammation. Moreover, and were positively correlated with immune-suppressive cells, inflammatory cytokines, immune checkpoint genes, and poor immunotherapy efficacy. Finally, the knockdown of and was observed to negatively affect the proliferation and migration of HepG2 cells in vitro. In conclusion, and are promising candidate biomarkers for the diagnosis, prognosis, and response to immunotherapy in HCC, and this study may help to understand the tumor microenvironment (TME) of liver cancer, and to develop new therapeutic targets.