Research Paper Volume 15, Issue 7 pp 2631—2666

Biological function analysis of ARHGAP39 as an independent prognostic biomarker in hepatocellular carcinoma

Yongqi Ding1,2, *, , Yiyang Gong2, *, , Hong Zeng2, *, , Xuanrui Zhou2, , Zichuan Yu2, , Jingying Pan2, , Minqin Zhou2, , Shiwen Liu3, , Wei Lai1, ,

  • 1 Department of Health Management Medical, The Second Affiliated Hospital of Nanchang University, Nanchang, China
  • 2 Second College of Clinical Medicine, Nanchang University, Nanchang, China
  • 3 Emergency Intensive Care Unit, The First Affiliated Hospital of Nanchang University, Nanchang, China
* Equal contribution

Received: January 1, 2023       Accepted: March 11, 2023       Published: April 5, 2023
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.


Hepatocellular carcinoma (HCC) is the most common subtype of liver cancer, with a high morbidity and low survival rate. Rho GTPase activating protein 39 (ARHGAP39) is a crucial activating protein of Rho GTPases, a novel target in cancer therapy, and it was identified as a hub gene for gastric cancer. However, the expression and role of ARHGAP39 in hepatocellular carcinoma remain unclear. Accordingly, the cancer genome atlas (TCGA) data were used to analyze the expression and clinical value of ARHGAP39 in hepatocellular carcinoma. Further, the LinkedOmics tool suggested functional enrichment pathways for ARHGAP39. To investigate in depth the possible role of ARHGAP39 on immune infiltration, we analyzed the relationship between ARHGAP39 and chemokines in HCCLM3 cells. Finally, the GSCA website was used to explore drug resistance in patients with high ARHGAP39 expression. Studies have shown that ARHGAP39 is highly expressed in hepatocellular carcinoma and relevant to clinicopathological features. In addition, the overexpression of ARHGAP39 leads to a poor prognosis. Besides, co-expressed genes and enrichment analysis showed a correlation with the cell cycle. Notably, ARHGAP39 may worsen the survival of hepatocellular carcinoma patients by increasing the level of immune infiltration through chemokines. Moreover, N6-methyladenosine (m6A) modification-related factors and drug sensitivity were also found to be associated with ARHGAP39. In brief, ARHGAP39 is a promising prognostic factor for hepatocellular carcinoma patients that is closely related to cell cycle, immune infiltration, m6A modification, and drug resistance.


ARHGAP39: a Rho GTP-activating protein 39; HCC: hepatocellular carcinoma; LIHC: liver hepatocellular carcinoma; TCGA: the cancer genome atlas; ICGC: international cancer genome consortium; LINC-JP: liver cancer – NCC JP datasets; 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; GTEx: the genotype-tissue expression; T: tumour size or extension, or both; N: regional lymph node involvement; M: distant metastasis; ROC: receiver operator characteristic curve; AUC: area under the curve; m6A: N6-methyladenosine; PD-1: programmed cell death protein-1; CTLA-4: cytotoxic T lymphocyte antigen 4; CCL20: C-C motif chemokine ligand 20; CXCL1: C-X-C motif chemokine ligand 1.