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

Frontiers in Oncology

Zhi-Hui Wang¹  Bin Zhao²  Wei-Hua Yan³  Yan Xia⁴  Yang Zhao⁵  Wen-Da Wang⁵  Guo-Yang Zheng⁵  Yu-Shi Zhang⁵ 

[1] Clinical College, Qingdao University, Qingdao, China;Department of Breast Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China;Department of Pathology, Affiliated Hospital of Qingdao University, Qingdao, China;Department of Pathology, Qilu Hospital, Shandong University, Qingdao, China;Department of Urology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China;

关键词: bladder cancer;    monocarboxylate transporter 4;    solute carrier family 16 member 3;    single-cell RNA sequencing;    immunohistochemistry;   

DOI  :  10.3389/fonc.2021.704857

来源: DOAJ

【 摘 要 】

BackgroundBladder 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 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.MethodsThe published single-cell RNA sequencing data of 49,869 bladder cancer cells and 15,827 normal bladder mucosa cells and The Cancer Genome Atlas (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. The Kaplan–Meier survival analysis and Cox regression were performed to analyze the association between MCT4 protein expression and OS in bladder cancer patients.ResultsSLC16A3 mRNA was upregulated in bladder cancer cells. The upregulated genes in SLC16A3-positive epithelial cells were enriched in the glycolysis process pathway and 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 the multivariate Cox analysis.ConclusionBladder 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.

【 授权许可】

Unknown