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 (ZNF385A) and zinc finger protein 346 (ZNF346) 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 ZNF385A and ZNF346, and their relationship with immune infiltration. Our results revealed that ZNF385A and ZNF346 were highly expressed and were associated with poor prognosis in HCC. Hepatitis B virus (HBV) infection may lead to the overexpression of ZNF385A and ZNF346, which was accompanied by elevated apoptosis and chronic inflammation. Moreover, ZNF385A and ZNF346 were positively correlated with immune-suppressive cells, inflammatory cytokines, immune checkpoint genes, and poor immunotherapy efficacy. Finally, the knockdown of ZNF385A and ZNF346 was observed to negatively affect the proliferation and migration of HepG2 cells in vitro. In conclusion, ZNF385A and ZNF346 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.

Automated summary

Hepatocellular carcinoma (HCC) is a deadly disease with limited diagnostic and therapeutic options. This study explored the expression and potential functions of ZNF385A and ZNF346 in HCC. The results showed that ZNF385A and ZNF346 were overexpressed in HCC and correlated with poor prognosis. They were also associated with immune infiltration and decreased response to immunotherapy. Knockdown of ZNF385A and ZNF346 inhibited HCC cell proliferation and migration. These findings suggest that ZNF385A and ZNF346 could be valuable biomarkers for HCC diagnosis, prognosis, and immunotherapy response.