Role and mechanism of PSMA4 in prognosis, diagnosis and immune infiltration of lung adenocarcinoma

Objective To investigate the role of PSMA4 in the prognosis, diagnosis and immune infiltration of lung adenocarcinoma (LUAD), and explore its underlying mechanism. Methods The expression profiles and clinical data of LUAD patients were sourced from the Cancer Genome Atlas (TCGA) database. The expression level of PSMA4 in LUAD tissues (n=539) and normal tissues (n=59) were compared using the Wilcoxon rank-sum test. The expression levels of PSMA4 in LUAD tissues and normal tissues were validated by analyzing the GSE40791 and GSE10072 LUAD datasets obtained from the Gene Expression Omnibus (GEO) database. In addition, tumor and adjacent non-cancerous tissues were collected from 10 LUAD undergoing lung biopsy by fiberoptic bronchoscopy in Second Affiliated Hospital of Army Medical University from January to December 2023. The PSMA4 expression in above samples was further verified using RT-qPCR. RT-qPCR was performed to detect the expression of PSMA4 in lung cancer cells and normal lung epithelial cells. Functional enrichment analysis and immune cell infiltration analysis were conducted on the cells with high and low expression of PSMA4. Cox regression analysis and Kaplan-Meier (KM) survival analysis were used to determine the diagnostic and prognostic value of PSMA4 for LUAD, and a nomogram was constructed to predict the overall survival rate at different time points. Results The analysis of TCGA datasets, GSE40791, and GSE10072 LUAD data revealed that PSMA4 expression was significantly higher in LUAD tissues than in normal tissues (P < 0.01). RT-qPCR further confirmed that the expression of PSMA4 was obviously elevated in LUAD tissues and lung cancer cells than adjacent non-cancerous tissues and normal lung epithelial cells (P < 0.01). High PSMA4 expression could be regarded as a marker for LUAD diagnosis and poor prognosis, and was associated with reduced proportions of Tem cells, TFH cells, B cells, NK cells, Tcm cells, and mast cells in the tumor microenvironment. Conclusion PSMA4 presents significant diagnostic performance for LUAD, and is closely associated with the prognosis and immune infiltration of this malignancy.