Prognostic and immunological roles of heat shock protein A4 in lung adenocarcinoma

Xuan Wu; Shen-Ying Yang; Yi-Hua Zhang; Jin-Zhou Fang; Shuai Wang; Zhi-Wei Xu; Xiao-Ju Zhang

doi:10.5306/wjco.v15.i1.45

Prognostic and immunological roles of heat shock protein A4 in lung adenocarcinoma

World J Clin Oncol. 2024 Jan 24;15(1):45-61. doi: 10.5306/wjco.v15.i1.45.

Authors

Xuan Wu¹, Shen-Ying Yang¹, Yi-Hua Zhang², Jin-Zhou Fang¹, Shuai Wang¹, Zhi-Wei Xu¹, Xiao-Ju Zhang³

Affiliations

¹ Department of Respiratory and Critical Care Medicine, Zhengzhou University People's Hospital, Zhengzhou 450008, Henan Province, China.
² Graduate School, Xinxiang Medical University, Xinxiang 453003, Henan Province, China.
³ Department of Pulmonary and Critical Care Medicine, Zhengzhou University People's Hospital, Zhengzhou 450008, Henan Province, China. zhangxiaoju@zzu.edu.cn.

Abstract

Background: Heat shock protein A4 (HSPA4) belongs to molecular chaperone protein family which plays important roles within variable cellular activities, including cancer initiation and progression. However, the prognostic and immunological significance of HSPA4 in lung adenocarcinoma (LUAD) has not been revealed yet.

Aim: To explore the prognostic and immunological roles of HSPA4 to identify a novel prognostic biomarker and therapeutic target for LUAD.

Methods: We assessed the prognostic and immunological significance of HSPA4 in LUAD using data from The Cancer Genome Atlas database. The association between HSPA4 expression and clinical-pathological features was assessed through Kruskal-Wallis and Wilcoxon signed-rank test. Univariate/multivariate Cox regression analyses and Kaplan-Meier curves were employed to evaluate prognostic factors, including HSPA4, in LUAD. Gene set enrichment analysis (GSEA) was conducted to identify the key signaling pathways associated with HSPA4. The correlation between HSPA4 expression and cancer immune infiltration was evaluated using single-sample gene set enrichment analysis (ssGSEA).

Results: Overexpressing HSPA4 was significantly related to advanced pathologic TNM stage, advanced pathologic stage, progression disease status of primary therapy outcome and female subgroups with LUAD. In addition, increased HSPA4 expression was found to be related to worse disease-specific survival and overall survival. GSEA analysis indicated a significant correlation between HSPA4 and cell cycle regulation and immune response, particularly through diminishing the function of cytotoxicity cells and CD8 T cells. The ssGSEA algorithm showed a positive correlation between HSPA4 expression and infiltrating levels of Th2 cells, while a negative correlation was observed with cytotoxic cell infiltration levels.

Conclusion: Our findings indicate HSPA4 is related to prognosis and immune cell infiltrates and may act as a novel prognostic biomarker and therapeutic target for LUAD.

Keywords: Heat shock protein A4; Lung adenocarcinoma; Prognosis; T helper cells; Tumor-infiltration.