Development and Validation of Prognostic Model in Transitional Bladder Cancer Based on Inflammatory Response-Associated Genes

Zhiwen Xie; Jinming Cai; Wenlan Sun; Shan Hua; Xingjie Wang; Anguo Li; Juntao Jiang

doi:10.3389/fonc.2021.740985

Development and Validation of Prognostic Model in Transitional Bladder Cancer Based on Inflammatory Response-Associated Genes

Front Oncol. 2021 Oct 7:11:740985. doi: 10.3389/fonc.2021.740985. eCollection 2021.

Authors

Zhiwen Xie¹, Jinming Cai¹, Wenlan Sun², Shan Hua¹, Xingjie Wang¹, Anguo Li³, Juntao Jiang¹

Affiliations

¹ Department of Urology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
² Department of Geriatrics, Shanghai General Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, China.
³ Department of Urology, The Fifth Peoples Hospital of Zunyi, Guizhou, China.

Abstract

Background: Bladder cancer is a common malignant type in the world, and over 90% are transitional cell carcinoma. While the impact of inflammatory response on cancer progression has been reported, the role of inflammatory response-associated genes (IRAGs) in transitional bladder cancer still needs to be understood.

Methods: In this study, IRAGs were download from Molecular Signature Database (MSigDB). The transcriptional expression and matched clinicopathological data were separately obtained from public databases. The TCGA-BLCA cohort was used to identify the differentially expressed IRAGs, and prognostic IRAGs were filtrated by univariate survival analysis. The intersection between them was displayed by Venn diagram. Based on least absolute shrinkage and selection operator (LASSO) regression analysis method, the TCGA-BLCA cohort was used to construct a risk signature. Survival analysis was conducted to calculate the overall survival (OS) in TCGA and GSE13507 cohort between two groups. We then conducted univariate and multivariate survival analyses to identify independently significant indicators for prognosis. Relationships between the risk scores and age, grade, stage, immune cell infiltration, immune function, and drug sensitivity were demonstrated by correlation analysis. The expression level of prognostic genes in vivo and in vitro were determined by qRT-PCR assay.

Results: Comparing with normal tissues, there were 49 differentially expressed IRAGs in cancer tissues, and 12 of them were markedly related to the prognosis in TCGA cohort for transitional bladder cancer patients. Based on LASSO regression analysis, a risk model consists of 10 IRAGs was established. Comparing with high-risk groups, survival analysis showed that patients in low-risk groups were more likely to have a better survival time in TCGA and GSE13507 cohorts. Besides, the accuracy of the model in predicting prognosis is acceptable, which is demonstrated by receiver operating characteristic curve (ROC) analysis. Age, stage, and risk scores variables were identified as the independently significant indicators for survival in transitional bladder cancer. Correlation analysis represented that the risk score was identified to be significantly related to the above variables except gender variable. Moreover, the expression level of prognostic genes in vivo and in vitro was markedly upregulated for transitional bladder cancer.

Conclusions: A novel model based on the 10 IRAGs that can be used to predict survival time for transitional bladder cancer. In addition, this study may provide treatment strategies according to the drug sensitivity in the future.

Keywords: drug sensitive; inflammatory response; prognostic model; qRT-PCR; risk score; transitional bladder carcinoma.