AUTHOR=Zhao Yang , Zhao Bin , Yan Wei-Hua , Xia Yan , Wang Zhi-Hui , Zheng Guo-Yang , Wang Wen-Da , Zhang Yu-Shi 

TITLE=Integrative Analysis Identified MCT4 as an Independent Prognostic Factor for Bladder Cancer

JOURNAL=Frontiers in Oncology

VOLUME=Volume 11 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2021.704857

DOI=10.3389/fonc.2021.704857

ISSN=2234-943X

ABSTRACT=Background: Bladder cancer is the 10th most common cancer and most common urothelial malignancy worldwide. Prognostic biomarkers for bladder cancer patients are required for individualized treatment. Monocarboxylate transporter-4(MCT4), encoded by the SLC16A3 gene, is a potential biomarker for bladder cancer because of its crucial role in the lactate efflux in the aerobic glycolysis process. We aimed to study the association between MCT4 expression and the overall survival (OS) of bladder cancer patients. 
Methods: The published single cell RNA sequencing data of 49,869 bladder cancer cells and 15,827 normal bladder mucosa cells and TCGA bladder cancer cohort data were used to explore the mRNA expression of SLC16A3 in bladder cancer. Eighty-nine consecutive bladder cancer patients who had undergone radical cystectomy were enrolled as a validation cohort. The expression of MCT4 proteins in bladder cancer specimens was detected using immunohistochemistry staining. Kaplan-Meier survival analysis and Cox regression were performed to analyze the association between MCT4 protein expression and OS in bladder cancer patients.
Results: SLC16A3 mRNA was upregulated in bladder cancer cells. The upregulated genes in SLC16A3-positive epithelial cells were enriched in the glycolysis process pathway, monocarboxylic acid metabolic process pathway. Patients with high SLC16A3 mRNA expression showed significantly poor OS (P = 0.016). High-MCT4 protein expression was also found to be an independent predictor for poor OS in bladder cancer patients (HR: 2.462; 95% CI: 1.202~5.042, P = 0.014). A nomogram was built based on the results of multivariate Cox analysis.
Conclusion: Bladder cancer with high SLC16A3 mRNA expression has a poor OS. High-MCT4 protein expression is an independent prognostic factor for bladder cancer patients who had undergone radical cystectomy.