Research Paper Volume 13, Issue 24 pp 25799—25845

DNA methylation of ARHGAP30 is negatively associated with ARHGAP30 expression in lung adenocarcinoma, which reduces tumor immunity and is detrimental to patient survival

Sheng Hu1, , Wenxiong Zhang1, , Jiayue Ye1, , Yang Zhang1, , Deyuan Zhang1, , Jinhua Peng1, , Dongliang Yu1, , Jianjun Xu1, , Yiping Wei1, ,

  • 1 Department of Thoracic Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, China

Received: July 5, 2021       Accepted: November 22, 2021       Published: December 15, 2021
How to Cite

Copyright: © 2021 Hu 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.


Rho-GTPase activating protein 30 (ARHGAP30) can enhance the intrinsic hydrolysis of GTP and regulates Rho-GTPase negatively. The relationship between ARHGAP30 expression and lung adenocarcinoma is unclear. Therefore, the present study aimed to assess the differences in expression of ARHGAP30 between lung adenocarcinoma tissues and normal tissues and the relationship between DNA methylation and ARHGAP30 expression in lung adenocarcinoma. To determine the role of ARHGAP30 expression in the prognosis and survival of patients with lung adenocarcinoma, gene set enrichment analysis of ARHGAP30 was performed, comprising analyses of Kyoto Encyclopedia of Genes and Genomes pathways, Panther pathways, Reactome pathways, Wikipathways, Gene Ontology, Kinase Target Network, Transcription Factor Network, and a protein-protein interaction network. The association of ARHGAP30 expression with tumor-infiltrating lymphocytes, immunostimulators, major histocompatibility complex molecules, chemokines, and chemokine receptors in lung adenocarcinoma tissues was also analyzed. DNA methylation of ARHGAP30 correlated negatively with ARHGAP30 expression. Patients with lung adenocarcinoma with high DNA methylation of ARHGAP30 had poor prognosis. The prognosis of patients with lung adenocarcinoma with low ARHGAP30 expression was also poor. ARHGAP30 expression in lung adenocarcinoma correlated positively, whereas methylation of ARHGAP30 correlated negatively, with levels of tumor infiltrating lymphocytes. Gene set enrichment analysis revealed that many pathways associated with ARHGAP30 should be studied to improve the diagnosis, treatment, and prognosis of lung adenocarcinoma. We speculated that DNA methylation of ARHGAP30 suppresses ARHGAP30 expression, which reduces tumor immunity, leading to poor prognosis for patients with lung adenocarcinoma.


ARHGAP30: Rho-GTPase activating protein 30; LUAD: lung adenocarcinoma; GSEA: gene set enrichment analysis; KEGG: Kyoto Encyclopedia of Genes and Genomes; PPI: protein-protein interaction; MHC: major histocompatibility complex; TILs: Tumor-Infiltrating Lymphocytes.