Clinical Eosinophil-Associated Genes can Serve as a Reliable Predictor of Bladder Urothelial Cancer

Chaojie Xu; Lishan Song; Hui Peng; Yubin Yang; Yi Liu; Dongchen Pei; Jianhua Guo; Nan Liu; Jiabang Liu; Xiaoyong Li; Chen Li; Zhengjun Kang

doi:10.3389/fmolb.2022.963455

Clinical Eosinophil-Associated Genes can Serve as a Reliable Predictor of Bladder Urothelial Cancer

Front Mol Biosci. 2022 Jul 22:9:963455. doi: 10.3389/fmolb.2022.963455. eCollection 2022.

Authors

Chaojie Xu¹, Lishan Song¹, Hui Peng², Yubin Yang³, Yi Liu¹, Dongchen Pei¹, Jianhua Guo¹, Nan Liu¹, Jiabang Liu³, Xiaoyong Li¹, Chen Li⁴, Zhengjun Kang¹

Affiliations

¹ The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, China.
² Department of Orthopaedics, Affiliated National Hospital of Guangxi Medical University, Nanning, China.
³ College of Pharmacy, Shantou University School of Medicine, Shantou, China.
⁴ Department of Biology, Chemistry, Pharmacy, Free University of Berlin, Berlin, Germany.

Abstract

Background: Numerous studies have shown that infiltrating eosinophils play a key role in the tumor progression of bladder urothelial carcinoma (BLCA). However, the roles of eosinophils and associated hub genes in clinical outcomes and immunotherapy are not well known. Methods: BLCA patient data were extracted from the TCGA database. The tumor immune microenvironment (TIME) was revealed by the CIBERSORT algorithm. Candidate modules and hub genes associated with eosinophils were identified by weighted gene co-expression network analysis (WGCNA). The external GEO database was applied to validate the above results. TIME-related genes with prognostic significance were screened by univariate Cox regression analysis, lasso regression, and multivariate Cox regression analysis. The patient's risk score (RS) was calculated and divided subjects into high-risk group (HRG) and low-risk group (LRG). The nomogram was developed based on the risk signature. Models were validated via receiver operating characteristic (ROC) curves and calibration curves. Differences between HRG and LRG in clinical features and tumor mutational burden (TMB) were compared. The Immune Phenomenon Score (IPS) was calculated to estimate the immunotherapeutic significance of RS. Half-maximal inhibitory concentrations (IC50s) of chemotherapeutic drugs were predicted by the pRRophetic algorithm. Results: 313 eosinophil-related genes were identified by WGCNA. Subsequently, a risk signature containing 9 eosinophil-related genes (AGXT, B3GALT2, CCDC62, CLEC1B, CLEC2D, CYP19A1, DNM3, SLC5A9, SLC26A8) was finally developed via multiplex analysis and screening. Age (p < 0.001), grade (p < 0.001), and RS (p < 0.001) were independent predictors of survival in BLCA patients. Based on the calibration curve, our risk signature nomogram was confirmed as a good predictor of BLCA patients' prognosis at 1, 3, and 5 years. The association analysis of RS and immunotherapy indicated that low-risk patients were more credible for novel immune checkpoint inhibitors (ICI) immunotherapy. The chemotherapeutic drug model suggests that RS has an effect on the drug sensitivity of patients. Conclusions: In conclusion, the eosinophil-based RS can be used as a reliable clinical predictor and provide insights into the precise treatment of BLCA.

Keywords: WGCNA; bladder urothelial carcinoma; eosinophil; immunotherapy; risk score.