Construction and verification of a novel hypoxia-related lncRNA signature related with survival outcomes and immune microenvironment of bladder urothelial carcinoma by weighted gene co-expression network analysis.

Abstract

Background: Bladder urothelial carcinoma (BLCA) is a common malignant tumor with the greatest recurrence rate of any solid tumor. Hypoxia is crucial in the growth and immune escape of malignant tumors. To predict clinical outcomes and immunological microenvironment of patients with BLCA, a hypoxia-related long non-coding RNA (HRlncRNA) signature was established. Methods: The Cancer Genome Atlas (TCGA) provided us with the differentially expressed profile of HRlncRNAs as well as clinical data from patients with BLCA, and we used weighted gene co-expression network analysis (WGCNA) to identify gene modules associated with malignancies. Results: Finally, Cox analysis revealed that HRlncRNAs, which comprised 13 lncRNAs, were implicated in the predictive signature. The training, testing, and overall cohorts of BLCA patients were divided into the low-risk group and high-risk group based on the median of the risk score. The Kaplan–Meier curves revealed that BLCA patients with a high-risk score had a poor prognosis, and the difference between subgroups was statistically significant. The receiver operating characteristic curves revealed that this signature outperformed other strategies in terms of predicting ability. Multivariate analysis revealed that the risk score was an independent prognostic index for overall survival (HR = 1.411; 1.259–1.582; p < 0.001). Then, a nomogram with clinicopathological features and risk score was established. This signature could effectively enhance the capacity to predict survival, according to the calibration plots, stratification, and clinical analysis. The majority of Kyoto Encyclopedia of Genes and Genomes (KEGG) were WNT, MAPK, and ERBB signaling pathways. Two groups had different immune cell subtypes, immune checkpoints, immunotherapy response, and anti-tumor drug sensitivity, which might result in differing survival outcomes. We then validated the differential expression of signature-related genes between tumor and normal tissues using TCGA paired data. Conclusion: This prognostic signature based on 13 HRlncRNAs may become a novel and potential prognostic biomarker, providing more accurate clinical decision-making and effective treatment for BLCA patients.