Integrative Analysis Identified MCT4 as an Independent Prognostic Factor for Bladder Cancer
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 ca...
Main Authors: | , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Frontiers Media S.A.
2021-08-01
|
Series: | Frontiers in Oncology |
Subjects: | |
Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2021.704857/full |
id |
doaj-aa098a9160e14b19b95edcee1c272e0b |
---|---|
record_format |
Article |
spelling |
doaj-aa098a9160e14b19b95edcee1c272e0b2021-08-26T04:51:48ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2021-08-011110.3389/fonc.2021.704857704857Integrative Analysis Identified MCT4 as an Independent Prognostic Factor for Bladder CancerYang Zhao0Bin Zhao1Wei-Hua Yan2Yan Xia3Zhi-Hui Wang4Guo-Yang Zheng5Wen-Da Wang6Yu-Shi Zhang7Department of Urology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaDepartment of Breast Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, ChinaDepartment of Pathology, Affiliated Hospital of Qingdao University, Qingdao, ChinaDepartment of Pathology, Qilu Hospital, Shandong University, Qingdao, ChinaClinical College, Qingdao University, Qingdao, ChinaDepartment of Urology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaDepartment of Urology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaDepartment of Urology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaBackgroundBladder 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.https://www.frontiersin.org/articles/10.3389/fonc.2021.704857/fullbladder cancermonocarboxylate transporter 4solute carrier family 16 member 3single-cell RNA sequencingimmunohistochemistry |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Yang Zhao Bin Zhao Wei-Hua Yan Yan Xia Zhi-Hui Wang Guo-Yang Zheng Wen-Da Wang Yu-Shi Zhang |
spellingShingle |
Yang Zhao Bin Zhao Wei-Hua Yan Yan Xia Zhi-Hui Wang Guo-Yang Zheng Wen-Da Wang Yu-Shi Zhang Integrative Analysis Identified MCT4 as an Independent Prognostic Factor for Bladder Cancer Frontiers in Oncology bladder cancer monocarboxylate transporter 4 solute carrier family 16 member 3 single-cell RNA sequencing immunohistochemistry |
author_facet |
Yang Zhao Bin Zhao Wei-Hua Yan Yan Xia Zhi-Hui Wang Guo-Yang Zheng Wen-Da Wang Yu-Shi Zhang |
author_sort |
Yang Zhao |
title |
Integrative Analysis Identified MCT4 as an Independent Prognostic Factor for Bladder Cancer |
title_short |
Integrative Analysis Identified MCT4 as an Independent Prognostic Factor for Bladder Cancer |
title_full |
Integrative Analysis Identified MCT4 as an Independent Prognostic Factor for Bladder Cancer |
title_fullStr |
Integrative Analysis Identified MCT4 as an Independent Prognostic Factor for Bladder Cancer |
title_full_unstemmed |
Integrative Analysis Identified MCT4 as an Independent Prognostic Factor for Bladder Cancer |
title_sort |
integrative analysis identified mct4 as an independent prognostic factor for bladder cancer |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Oncology |
issn |
2234-943X |
publishDate |
2021-08-01 |
description |
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. |
topic |
bladder cancer monocarboxylate transporter 4 solute carrier family 16 member 3 single-cell RNA sequencing immunohistochemistry |
url |
https://www.frontiersin.org/articles/10.3389/fonc.2021.704857/full |
work_keys_str_mv |
AT yangzhao integrativeanalysisidentifiedmct4asanindependentprognosticfactorforbladdercancer AT binzhao integrativeanalysisidentifiedmct4asanindependentprognosticfactorforbladdercancer AT weihuayan integrativeanalysisidentifiedmct4asanindependentprognosticfactorforbladdercancer AT yanxia integrativeanalysisidentifiedmct4asanindependentprognosticfactorforbladdercancer AT zhihuiwang integrativeanalysisidentifiedmct4asanindependentprognosticfactorforbladdercancer AT guoyangzheng integrativeanalysisidentifiedmct4asanindependentprognosticfactorforbladdercancer AT wendawang integrativeanalysisidentifiedmct4asanindependentprognosticfactorforbladdercancer AT yushizhang integrativeanalysisidentifiedmct4asanindependentprognosticfactorforbladdercancer |
_version_ |
1721196025873432576 |