Construction and validation of a gene signature related to bladder urothelial carcinoma based on immune gene analysis

Abstract

BackgroundThis study developed a gene signature associated with a malignant and common tumor of the urinary system, the Bladder Urothelial Carcinoma (BLCA).MethodsThe Cancer Genome Atlas (TCGA) database was searched to obtain 414 BLCA samples and the expression spectra of 19 normal samples. Single-sample Gene Set Enrichment Analysis (ssGSEA) was conducted to determine the enrichment levels in the BLCA samples of the 29 immune genes. Unsupervised hierarchical clustering, gene set enrichment analysis (GSEA), single-factor Cox analysis, least absolute shrinkage and selection operator (LASSO) regression models, and GEO queues were used to determine the BLCA immune gene subtype, analyze the biological pathway differences between immune gene subtypes, determine the characteristic genes of BLCA associated with prognosis, identify the BLCA-related genes, and verify the gene signature, respectively.ResultsWe identified two immune gene subtypes (immunity_L and immunity_H). The latter was significantly related to receptors, JAK STAT signaling pathways, leukocyte interleukin 6 generation, and cell membrane signal receptor complexes. Four characteristic genes (RBP1, OAS1, LRP1, and AGER) were identified and constituted the gene signature. Significant survival advantages, higher mutation frequency, and superior immunotherapy were observed in the low-risk group patients. The gene signature had good predictive ability. The results of the validation group were consistent with TCGA queue results.ConclusionsWe constructed a 4-gene signature that helps monitor BLCA occurrence and prognosis, providing an important basis for developing personalized BLCA immunotherapy.