A robust eleven-genes prognostic model can predict overall survival in bladder cancer patients based on five cohorts

Abstract

Background: Bladder cancer is the tenth most common cancer globally, but existing biomarkers and prognostic models are limited.

Method: In this study, we used four bladder cancer cohorts from The Cancer Genome Atlas and Gene Expression Omnibus databases to perform univariate Cox regression analysis to identify common prognostic genes. We used the least absolute shrinkage and selection operator regression to construct a prognostic Cox model. Kaplan-Meier analysis, receiver operating characteristic curve, and univariate / multivariate Cox analysis were used to evaluate the prognostic model for the four cohorts. Finally, a co-expression network, CIBERSORT, and ESTIMATE algorithm were used to explore the mechanism related to the model.

Results: A total of 11 genes were identified from the four cohorts to construct the prognostic model, including eight risk genes (SERPINE2, PRR11, DSEL, DNM1, COMP, ELOVL4, RTKN, and MAPK12) and three protective genes (FABP6, C16orf74, and TNK1). The 11-genes model could stratify the risk of patients in all five cohorts, and the prognosis was worse in the group with a high-risk score. The area under the curve values of the five cohorts in the first year are all greater than 0.65. Furthermore, this model's predictive ability is stronger than that of age, gender, grade, and T stage. Through the weighted co-expression network analysis, the gene module related to the model was found, and the key genes in this module were mainly enriched in the tumor microenvironment. B cell memory showed low infiltration in high-risk patients. Furthermore, in the case of low B cell memory infiltration and high-risk score, the prognosis of the patients was the worst.

Conclusion: The proposed eleven-genes model is a promising biomarker for estimating overall survival in bladder cancer. This model can be used to stratify the risk of bladder cancer patients, which is beneficial to the realization of individualized treatment.