Abstract
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.
Highlights
Bladder cancer is the 10th most common cancer and most common urothelial malignancy worldwide, with approximately 573,000 new cases and 213,000 deaths per year [1]
65,723 filtered cells were used for bioinformatics analysis, including 49,869 bladder cancer cells and 15,827 cells from the normal bladder mucosa (NBM) (Figure 1A)
Granulocytes were identified by GATA2, and macrophages were marked by CD68 expression (Figure 1C)
Summary
Bladder cancer is the 10th most common cancer and most common urothelial malignancy worldwide, with approximately 573,000 new cases and 213,000 deaths per year [1]. Prognostic biomarkers for bladder cancer patients are needed for more individualized surveillance and intervention after surgery. In contrast to normal cells, which rely on oxidative phosphorylation to generate the energy needed for cellular processes, cancer cells rely on glycolysis for the energy needed for survival and proliferation [6]. This phenomenon is termed aerobic glycolysis or the Warburg effect, which is common among human malignancies [6, 7]. 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
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