Risk stratification based on immune signature and prediction of immune checkpoint inhibitor’s efficacy for bladder urothelial carcinoma

Abstract

Abstract Purpose：To investigate the impact of the tumor immune microenvironment on survival and response to immune checkpoint inhibitors (ICIs) in patients with bladder urothelial carcinoma (BLCA). Materials and Methods: We constructed a prognostic immune signature based on the TCGA dataset and verified its predictive accuracy on both internal and total data sets. Firstly, we screened immune genes associated with prognosis based on univariate Cox risk regression analysis. Secondly, LASSO model is used for variable selection and regularization to avoid over-fitting. Thirdly, we also carried out immune status or immunophenoscore (IPS) analysis. Immune genes used in constructing a immune-related multivariate Cox risk regression analysis, and univariate and multivariate Cox regression analysis is used to evaluate the performance of high-risk and low-risk groups in tumor mutation load, patients' response to ICI treatment, tumor infiltrating lymphocytes and other aspects. Results: This immunomarker consists of 6 immune-related genes, which we confirmed to be an independent prognostic element for BLCA patients. We found that patients in the high-risk group had poorer overall survival, while patients in the low-risk group had better overall survival. Although the difference was not significant, high-risk score patients had fewer mast cell rest and neutrophils, and more memory activation of b cell infants and t cell CD4, which was closely associated with clinical outcome. In addition, the tumor mutational burden (TMB) was significantly reduced in the low-risk group. When using IPS as a substitute for ICI response, we found that patients with low-risk scores had significantly higher IPS. Conclusion: Our study concluded that 6 immune-related genes signature may be related to prognosis and prediction of ICI treatment, but further verification is needed.