The role of ARL4C in predicting prognosis and immunotherapy drug susceptibility in pan-cancer analysis

Hanshu Zhao; Kaiqi Yang; Ziqi Yue; Ziyin Chen; Zhe Cheng; Hongcheng Sun; Changze Song

doi:10.3389/fphar.2023.1288492

The role of ARL4C in predicting prognosis and immunotherapy drug susceptibility in pan-cancer analysis

Front Pharmacol. 2023 Dec 20:14:1288492. doi: 10.3389/fphar.2023.1288492. eCollection 2023.

Authors

Hanshu Zhao^#^{1

2}, Kaiqi Yang^#³, Ziqi Yue^#⁴, Ziyin Chen⁵, Zhe Cheng⁴, Hongcheng Sun⁶, Changze Song^{1

7}

Affiliations

¹ Scientific Research Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China.
² Department of Neurology, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
³ Clinical Medicine, Harbin Medical University, Harbin, China.
⁴ Department of Forensic Medicine, Harbin Medical University, Harbin, China.
⁵ Department of Urology, China-Japan Friendship Hospital, Beijing, China.
⁶ Department of Gastroenterology, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
⁷ Department of Urology, The Fourth Hospital of Harbin Medical University, Harbin, China.

^# Contributed equally.

Abstract

Background: ARLs, which are a class of small GTP-binding proteins, play a crucial role in facilitating tumor tumorigenesis and development. ARL4C, a vital member of the ARLs family, has been implicated in the progression of tumors, metastatic dissemination, and development of resistance to therapeutic drugs. Nevertheless, the precise functional mechanisms of ARL4C concerning tumor prognosis and immunotherapy drug susceptibility remain elusive. Methods: By combining the GTEx and TCGA databases, the presence of ARL4C was examined in 33 various types of cancer. Immunohistochemistry and immunofluorescence staining techniques were utilized to confirm the expression of ARL4C in particular tumor tissues. Furthermore, the ESTIMATE algorithm and TIMER2.0 database were utilized to analyze the tumor microenvironment and immune infiltration associated with ARL4C. The TISCH platform facilitated the utilization of single-cell RNA-seq datasets for further analysis. ARL4C-related immune escape was investigated using the TISMO tool. Lastly, drug sensitivity analysis was conducted to assess the sensitivity of different types of tumors to compounds based on the varying levels of ARL4C expression. Results: The study found that ARL4C was highly expressed in 23 different types of cancer. Moreover, the presence of high ARL4C expression was found to be associated with a poor prognosis in BLCA, COAD, KIRP, LGG, and UCEC. Notably, ARL4C was also expressed in immune cells, and its high expression was found to be correlated with cancer immune activation. Most importantly, the drug sensitivity analysis revealed a positive correlation between ARL4C expression and the heightened sensitivity of tumors to Staurosporine, Midostaurin, and Nelarabine. Conclusion: The findings from our study indicate that the expression level of ARL4C may exert an influence on cancer development, prognosis, and susceptibility to immunotherapy drugs. In addition, the involvement of ARL4C in the tumor immune microenvironment has expanded the concept of ARL4C-targeted immunotherapy.

Keywords: ARL4C; immunotherapy drug susceptibility; pan-cancer; prognosis; tumor microenvironment.

Grants and funding

The author(s) declare that no financial support was received for the research, authorship, and/or publication of this article.