Research Paper Volume 15, Issue 13 pp 6179—6211

ZNF765 is a prognostic biomarker of hepatocellular carcinoma associated with cell cycle, immune infiltration, m6A modification, and drug susceptibility

Yongqi Ding1,2, *, , Yiyang Gong2, *, , Hong Zeng2, , Gelin Song2, , Zichuan Yu2, , Bidong Fu2, , Yue Liu2, , Da Huang3, , Yanying Zhong4, ,

  • 1 Second Affiliated Hospital of Nanchang University, Nanchang, China
  • 2 Second College of Clinical Medicine, Nanchang University, Nanchang, China
  • 3 Department of Thyroid Surgery, Second Affiliated Hospital of Nanchang University, Nanchang, China
  • 4 Department of Obstetrics and Gynecology, Second Affiliated Hospital of Nanchang University, Nanchang, China
* Equal contribution

Received: September 21, 2022       Accepted: June 5, 2023       Published: July 4, 2023      

https://doi.org/10.18632/aging.204827
How to Cite

Copyright: © 2023 Ding et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Hepatocellular carcinoma (HCC) is an ongoing challenge worldwide. Zinc finger protein 765 (ZNF765) is an important zinc finger protein that is related to the permeability of the blood-tumor barrier. However, the role of ZNF765 in HCC is unclear. This study evaluated the expression of ZNF765 in hepatocellular carcinoma and the impact of its expression on patient prognosis based on The Cancer Genome Atlas (TCGA). Immunohistochemical assays (IHC) were used to examine protein expression. Besides, a colony formation assay was used to examine cell viability. We also explored the relationship between ZNF765 and chemokines in the HCCLM3 cells by qRT-PCR. Moreover, we examined the effect of ZNF765 on cell resistance by measurement of the maximum half-inhibitory concentration. Our research revealed that ZNF765 expression in HCC samples was higher than that in normal samples, whose upregulation was not conducive to the prognosis. The results of GO, KEGG, and GSEA showed that ZNF765 was associated with the cell cycle and immune infiltration. Furthermore, we confirmed that the expression of ZNF765 had a strong connection with the infiltration level of various immune cells, such as B cells, CD4+ T cells, macrophages, and neutrophils. In addition, we found that ZNF765 was associated with m6A modification, which may affect the progression of HCC. Finally, drug sensitivity testing found that patients with HCC were sensitive to 20 drugs when they expressed high levels of ZNF765. In conclusion, ZNF765 may be a prognostic biomarker related to cell cycle, immune infiltration, m6A modification, and drug sensitivity for hepatocellular carcinoma.

Abbreviations

ZNF765: zinc finger protein 765; HCC: hepatocellular carcinoma; LIHC: liver hepatocellular carcinoma; ICH: immunohistochemical; ZNF: zinc finger; TCGA: the cancer genome atlas; ICGC: international cancer genome consortium; LINC-JP: liver cancer - NCC, JP datasets; GEO: gene expression omnibus; TCGA-LIHC: liver hepatocellular carcinoma project of cancer genome atlas; ICGC LIRI-JP: liver cancer-RIKEN, and JP project from international cancer genome consortium; OS: overall survival; PFS: progression-free survival; DSS: disease-specific survival; RFS: relapse-free survival; HRs: hazard ratios; GO: gene ontology; KEGG: Kyoto encyclopedia of genes and genomes; GSEA: gene set enrichment analysis; GEPIA: gene expression profiling interactive analysis; GTEx: the genotype-tissue expression; RT-PCR: real-time PCR; T: tumor size; N: lymph node metastasis; ROC: receiver operator characteristic curve; AUC: area under the curve; SCNA: somatic copy number alteration; m6A: N6-methyladenosine; TME: tumor microenvironment; NETs: neutrophil extracellular traps; PD-1: programmed cell death 1; PD-L1: programmed cell death ligand 1; CTLA-4: cytotoxic T lymphocyte antigen 4.