Database Mining of Genes of Prognostic Value for the Prostate Adenocarcinoma Microenvironment Using the Cancer Gene Atlas

Abstract

Background. Prostate adenocarcinoma (PRAD) is a common malignant tumor in elderly men. Our research uses The Cancer Gene Atlas (TCGA) database to find potential related genes for predicting the prognosis of patients with PRAD. Methods. We downloaded gene expression profiles and clinical sample information from TCGA for 490 patients with PRAD (patient age: 41-78 years). We calculated stromal and immune scores using the ESTIMATE algorithm to predict the level of stromal and immune cell infiltration. We categorized patients with PRAD in TCGA into high and low score arrays according to their median immune/stromal scores and identified differentially expressed genes (DEGs) that were significantly correlated with the prognosis of PRAD. Then, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed. The association between DEGs and overall survival was investigated by weighted Kaplan–Meier survival analysis and multivariate analysis. Furthermore, the protein-protein interaction network (PPI) of DEGs was constructed using the STRING tool. Finally, the hub genes were identified by analyzing the degree of association of PPI networks. Results. We found that 8 individual DEGs, C6, S100A12, MLC1, PAX5, C7, FAM162B, CAMK1G, and TCEAL5, were significantly predictive of favorable overall survival and one DEG, EPYC, was associated with poor overall survival. GO and KEGG pathway analyses revealed that the DEGs were associated with immune responses. Moreover, 30 hub genes were obtained using the PPI network of DEGs: ITGAM, CD4, CD3E, IL-10, LCP2, ITGB2, ZAP-70, C3, CCL19, CXCL13, CXCL9, BTK, CCL21, CD247, CD28, CD3D, FCER1G, PTPRC, TYROBP, CCR5, ITK, CCL13, CCR1, CCR2, CD79B, CYBB, IL2RG, JAK3, PLCG2, and CD19. These prominent nodes had the most associations with other genes, indicating that they might play crucial roles in the prognosis of PRAD. Conclusions. We extracted a list of genes associated with the prostate adenocarcinoma microenvironment, which might contribute to the prediction and interpretation of PRAD prognosis.