Expression and Prognostic Significance of the Nicotinic Receptor Cluster on 15q25 about CHRNA5 and PSMA4 mRNA in Lung Adenocarcinoma Utilizing TCGA Datasets

Abstract

Background: Genome-wide association studies of lung cancer have shown a common variation at 15q24-25.1 as a determinant of risk, but the role of specific genes has not been proven. This study aims to explore the expression of mutations and the prognostic significance of 15q25 (CHRNA5 and PSMA4) mRNA in lung adenocarcinoma (LAC) based on immunohistochemistry, TCGA and bioinformatics. Methods: The expression of mutations on chromosome 15q25 of 576 primary LAC patients was selected and survival and gene expression data were extracted from TCGA. The relationship between expression of genes on 15q25 and clinical and prognostic Significance of LAC. An experiment with Beas-2b, A549 and H1299 cell lines was performed to further prove the difference in CHRNA5 and PSMA4 expression between lung cancer and normal cells. Immunohistochemistry data of CHRNA5 and PSMA4 were detected in LAC and normal tissues from 122 patients. Finally, Gene enrichment analysis (GSEA) was conducted to predict the regulatory genes of CHRNA5 and PSMA4. Results: CHRNA5 and PSMA4 are frequently mutated in TCGA (CHRNA5, 1.7%; PSMA4, 1.3%). Besides, the expression of CHRNA5 and PSMA4 was obviously higher in A549 and H1299 cells. And the immunohistochemical staining revealed that the levels of CHRNA5 and PSMA4 were considerably higher in the LAC group than in the normal group. Meanwhile, there was a significant association between high CHRNA5 expression and smoking history (P=0.011), smoking history pack year value (P=0.010). Furthermore, there was a significant correlation between CHRNA5 and PSMA4 expression levels and prognosis (P=0.003; P=0.008), and between higher expression and worse prognosis. GSEA results suggested that between samples with high CHRNA5 and PSMA4 expression were respectively enriched to cell cycle, base excision repair, oxidative phosphorylation, protein export, and aminoacyl tRNA biosynthesis, among others. Conclusions: CHRNA5 and PSMA4 mRNA expression has a significant impact on the clinical and survival of LAC, and they may be a potential target for treating patients with lung adenocarcinoma.