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

Abstract

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.

DNA methylation alterations of ADCY5, MICAL2, and PLEKHG2 during the developmental stage of cryptogenic hepatocellular carcinoma

“…This is consistent with a previous report that RAB3D is upregulated in HCC cells and enhances the malignant phenotype of HCCs through the Warburg effect 39 . A transcription factor, ZNF3 85A , showed DNA hypomethylation in U III ‐N samples, and may be upregulated during U III ‐T development, which is consistent with a previous report that overexpression of ZNF3 85A in HCCs is associated with poorer prognosis 40 . ARHGEF2 , a Rho/Rac guanine nucleotide exchange factor, again shows DNA hypomethylation in U III ‐N samples, which is consistent with a previous report that ARHGEF2 overexpression is associated with malignant progression of HCCs 41 .…”

Integrated single-cell and bulk RNA-seq analysis reveals a novel T-cell signature for prognosis and treatment response in colorectal cancer

“…Studies have reported that downregulating ADAM8 in colorectal cancer cells enhances the cytotoxic effect of tumor-in ltrating lymphocytes 40 . ZNF385A has been identi ed as a gene associated with lymphatic vessel formation in CRC, in uencing immune cell in ltration, and is also associated with an immunosuppressive phenotype in HCC 41,42 . G0S2 is linked to evasion from cytotoxic T lymphocytes and knocking down G0S2 signi cantly inhibits proliferation and migration of CRC cell lines 43 .…”

Quantitative Proteomics Reveal the Mechanism of MiR-138–5p Suppressing Cervical Cancer via Targeting ZNF385A

“…CCK-8, transwell, and wound healing assays were performed to measure cell proliferation and migration as described previously. 30…”