The prognostic roles of CYP19A1 expression in bladder cancer patients of different genders

Shanghua Cai; Yuanfa Feng; Jianheng Ye; Yulin Deng; Zhiduan Cai; Xuejin Zhu; Ren Liu; Yixun Zhang; Zhihao Zou; Zhenfeng Tang; Zhaodong Han; Chi Tin Hon; Weide Zhong; Huichan He

doi:10.21037/tau-21-400

The prognostic roles of CYP19A1 expression in bladder cancer patients of different genders

Transl Androl Urol. 2021 Sep;10(9):3579-3590. doi: 10.21037/tau-21-400.

Authors

Shanghua Cai¹, Yuanfa Feng¹, Jianheng Ye², Yulin Deng¹, Zhiduan Cai³, Xuejin Zhu¹, Ren Liu², Yixun Zhang², Zhihao Zou², Zhenfeng Tang¹, Zhaodong Han², Chi Tin Hon⁴, Weide Zhong^{1

2

5

6}, Huichan He¹

Affiliations

¹ Department of Urology, Guangdong Key Laboratory of Urology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, China.
² Department of Urology, Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, China.
³ Department of Urology, The Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
⁴ Macau Institute of Systems Engineering, Macau University of Science and Technology, Macau, China.
⁵ Department of Urology, Huizhou Municipal Central Hospital, Huizhou, China.
⁶ Macau Institute for Applied Research in Medicine and Health, Macau University of Science and Technology, Macau, China.

Abstract

Background: The incidence of bladder cancer (BCa) in male is approximately three to four times higher than in female, but the oncological outcomes in female patients with BCa are significantly worse than in male patients. Although many biomarkers have been identified in recent decades to predict the prognosis of BCa patients, few of them are able to distinguish the prognosis of BCa patients with gender difference. Aromatase encoded by the CYP19A1 gene catalyzes the conversion of androgens to estrogens. In this study, we investigate the prognosis significance of CYP19A1 expression considering the gender difference in BCa patients from four available public databases.

Methods: Four available public databases of BCa, including GSE13507, TCGA-BLCA, E-MTAB-4321, and E-MTAB-1803, were utilized in this analysis. The overall survival (OS) and progression-free survival (PFS) in different stages and genders were evaluated using the Kaplan-Meier analysis based on the optimal cut-off values of CYP19A1 expression. Then, Gene Set Enrichment Analysis (GSEA) were further performed to explore the potential biologic pathways by altering CYP19A1 expression in BCa patients.

Results: The results showed that patients with high CYP19A1 expression had a poorer outcome compared with those with low expression in both BCa cohorts in general. Higher CYP19A1 expression in male patients were significantly associated with shorter survival for either non-muscle-invasive bladder cancer (NMIBC) or muscle-invasive bladder cancer (MIBC). However, female NMIBC patients with high CYP19A1 expression were identified to have a better prognosis, whereas high CYP19A1 expression in female MIBC patients were significantly associated with poorer survival. The result of the GSEA showed that different outcomes in female and male patients with NMIBC were related to the interaction of CYP19A1 and the cell-cycle-related pathways.

Conclusions: These findings demonstrated that CYP19A1 expression might have a potential role in distinguishing the prognosis of female BCa patients dependent on tumor stage. Our results provide new insights for aromatase-mediated BCa therapy.

Keywords: CYP19A1; bioinformatics analysis; bladder cancer (BCa); gender difference; prognosis.