Research Paper|Volume 15, Issue 7|pp 2631—2666

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

Yongqi Ding^1,², Yiyang Gong², Hong Zeng², Xuanrui Zhou², Zichuan Yu², Jingying Pan², Minqin Zhou², Shiwen Liu³, Wei Lai¹

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

* Equal contribution

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

https://doi.org/10.18632/aging.204635

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 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.