Abstract：Objective To study the expression and clinical significance of heat shock protein A4 (HSPA4) in lung adenocarcinoma by bioinformatics.Methods The data of TCGA and GEO were downloaded, and the expression difference of HSPA4 gene in lung adenocarcinoma and adjacent tissues was analyzed by R software; the differences of protein expression between lung adenocarcinoma and normal lung tissue were compared with HPA database; the diagnostic and prognostic value of HSPA4 expression in lung adenocarcinoma and the correlation between HSPA4 expression and various immune cells in tumor microenvironment were analyzed by ROC curve, time-dependent ROC curve, nomogram and correlation analysis. The STRING database was used to establish HSPA4 related protein interaction network, and GO, KEGG and GSEA databases were used to analyze the potential functions of HSPA4 and its interaction proteins in lung adenocarcinoma.Results In the data sets of TCGA-LUAD, GSE43448 and GSE10072, the expression of HSPA4 in lung adenocarcinoma was higher than that in normal lung tissues and adjacent tissues (P<0.001), and the expression of HSPA4 in lung adenocarcinoma was significantly higher. High expression of HSPA4 was associated with TNM and pathological stages of lung adenocarcinoma; ROC diagram showed that HSPA4 had good diagnostic value (AUC=0.810). The time dependent ROC chart showed that the AUC of 1 year, 3 years and 5 years were 0.605, 0.583 and 0.553 respectively. The nomogram showed that HSPA4, together with other clinical factors, had a good predictive value for 1-year, 3-year and 5-year survival rates. K-M diagram showed that the high expression of HSPA4 was related with the poor prognosis of lung adenocarcinoma patients. The change rate of HSPA4 gene was 2.2%. Three methylation sites were associated with the prognosis of lung adenocarcinoma. In TME, HSPA4 expression was positively correlated with Th2, T helper cells and other immune cells; It was negatively correlated with B cells, pDC, CD8 T cells, Cytotoxic cells, NK CD56bright cells, T cells and other immune cells. PPI protein interaction showed that HSPA4 interacted with HSP90AA1, SNCA and other proteins. Enrichment analysis of GO, KEGG, GSEA pathways showed that HSPA4 had the functions of antigen processing and presenting, and regulating immunity.Conclusions HSPA4 is highly expressed in lung adenocarcinoma, and its expression level is related with the overall prognosis of lung adenocarcinoma patients. It also participates in the occurrence and development of tumor, and affects the tumor microenvironment, which may become a new biomarker and therapeutic target in lung adenocarcinoma.
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2023, Vol. 34 
