Establishment and Validation of a Tumor Microenvironment Prognostic Model for Predicting Bladder Cancer Survival Status Based on Integrated Bioinformatics Analyses.

Abstract

This study was designed to analyze the characteristics of bladder cancer-related genes and establish a prognostic model of bladder cancer. The model passed an independent external validation set test. Differentially expressed genes (DEGs) related to bladder cancer were obtained from the Gene Expression Omnibus (GEO), The Cancer Genome Atlas (TCGA), and Genotype-Tissue Expression (GTEx) databases. WGCNA was used to fit the GSE188715, TCGA, and GTEx RNA-Seq data. Fusing the module genes with the high significance in tumor development extracted from WGCNA and DEGs screened from multiple databases. 709 common prognostic-related genes were obtained. The 709 genes were enriched in the Gene Ontology database. Univariate Cox and LASSO regression analyses were used to screen out 21 prognostic-related genes and further multivariate Cox regression established a bladder cancer prognostic model consisting of 8 genes. After the eight-gene prognostic model was established, the Human Protein Atlas (HPA) database, GEPIA 2, and quantitative real-time PCR (qRT-PCR) verified the differential expression of these genes. Gene Set Enrichment Analysis and immune infiltration analysis found biologically enrichment pathways and cellular immune infiltration related to this bladder cancer prognostic model. Then, we selected bladder cancer patients in the TCGA database to evaluate the predictive ability of the model on the training set and validation set. The overall survival status of the two TCGA patient groups in the training and the test sets was obtained by Kaplan–Meier survival analysis. Three-year survival rates in the training and test sets were 37.163% and 25.009% for the low-risk groups and 70.000% and 62.235% for the high-risk groups, respectively. Receiver operating characteristic curve (ROC) analysis showed that the areas under the curve (AUCs) for the training and test sets were above 0.7. In an external independent validation database GSE13507, Kaplan–Meier survival analysis showed that the three-year survival rates of the high-risk and the low-risk groups in this database were 56.719% and 76.734%, respectively. The AUCs of the ROC drawn in the external validation set were both above 0.65. Here, we constructed a prognostic model of bladder cancer based on data from the GEO, TCGA, and GTEx databases. This model has potential prognostic and clinical auxiliary diagnostic value.