Clinical neutrophil-related gene helps treat bladder urothelial carcinoma

Abstract

Abstract Objectives Most researches have shown that neutrophils are closely related to bladder urothelial carcinoma (BLCA), especially its occurrence and development. Although tumor microenvironment (TME) related genes have an impact on prognosis, the role of neutrophil related genes in BLCA adjuvant therapy is not clear. Methods We used sample information from The Cancer Genome Atlas and Gene Expression Omnibus (GEO) databases. And we utilized the CIBERSORT algorithm to obtain the tumor immune microenvironment (TIME) landscape and weighted gene co-expression network analysis (WCGNA) to detect neutrophil-related gene modules. We used univariate Cox regression, multivariate Cox regression, and lasso regression analyses to identify genes that have a relationship with BLCA prognosis. Using the median risk score (RS), we classified the cohort into a high-risk group (HRG) and low-risk group (LRG). External validation of RS was performed via GEO data feeds. Prognostic nomograms were constructed with reference to RS and clinically relevant information and validated using calibration curves. We analyzed the latent connections between RS and tumor mutational burden. Finally, the latent associations between risk markers and chemotherapy prognosis were explored using the pRRophetic algorithm. Results In this study, 10 TME-related genes with important prognostic value were screened. Then, by deriving the RS, we constructed a prognostic risk prediction nomogram using parameters such as sex, age, TNM stage, clinical stage, and RS. The area under the receiver operating characteristic curve showed that the predictive accuracy of the constructed nomogram was high. We found that using immunotherapy with new immune checkpoint inhibitors (ICIs) was more beneficial for patients in the LRG. In addition, we can learn from the chemotherapeutic drug model that patients with LRG are more sensitive to cisplatin and imatinib. Conclusions In short, the prognostic prediction model based on neutrophil-related genes will help to predict the prognosis and guide the precise treatment of BLCA.