Clinical and Translational Research
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Oncol. Jan 24, 2024; 15(1): 45-61
Published online Jan 24, 2024. doi: 10.5306/wjco.v15.i1.45
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
Xuan Wu, Shen-Ying Yang, Jin-Zhou Fang, Shuai Wang, Zhi-Wei Xu, Department of Respiratory and Critical Care Medicine, Zhengzhou University People’s Hospital, Zhengzhou 450008, Henan Province, China
Yi-Hua Zhang, Graduate School, Xinxiang Medical University, Xinxiang 453003, Henan Province, China
Xiao-Ju Zhang, Department of Pulmonary and Critical Care Medicine, Zhengzhou University People’s Hospital, Zhengzhou 450008, Henan Province, China
Author contributions: Wu X and Yang SY contributed equally to this work; Wu X, Yang SY and Zhang XJ designed the research study; Wu X, Yang SY and Fang JZ performed the analysis; Wu X, Yang SY, and Wang S analyzed the data and wrote the manuscript; all authors have read and approve the final manuscript.
Institutional review board statement: This study was reviewed and approved by the Ethics Committee of Zhengzhou University People’s Hospital.
Clinical trial registration statement: Since our paper is not a clinical research study but a bioinformatics analysis to assess the prognostic and immunological significance of HSPA4 in LUAD using data from public database. So, it is not applicable to provide the Clinical Trial Registration Statement.
Informed consent statement: Since our paper is not a clinical research study but a bioinformatics analysis to assess the prognostic and immunological significance of HSPA4 in LUAD using data from public database. So, it is not applicable to provide the Signed Informed Consent Form(s) or Document(s).
Conflict-of-interest statement: All the authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Data sharing statement: The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/Supplementary material.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Xiao-Ju Zhang, Doctor, PhD, Academic Research, Additional Professor, Chief Physician, Department of Pulmonary and Critical Care Medicine, Zhengzhou University People’s Hospital, No. 7 Weiwu Road, Jinshui District, Zhengzhou 450008, Henan Province, China. zhangxiaoju@zzu.edu.cn
Received: September 11, 2023
Peer-review started: September 11, 2023
First decision: November 23, 2023
Revised: December 3, 2023
Accepted: December 29, 2023
Article in press: December 29, 2023
Published online: January 24, 2024
Processing time: 133 Days and 23.3 Hours
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; Tumor-infiltration; Prognosis; T helper cells

Core Tip: Overexpressing heat shock protein A4 (HSPA4) was significantly related to advanced pathologic TNM stage, advanced pathologic stage, progression disease status of primary therapy outcome and female subgroups with lung adenocarcinoma. In addition, increased HSPA4 expression was also found to be related to worse disease-specific survival and overall survival. Gene set enrichment 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 single-sample gene set enrichment analysis 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.