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A glycolysis-based 4-mRNA signature correlates with the prognosis and cell cycle process in patients with bladder cancer
BACKGROUND: Bladder cancer is one of the most prevalent malignancies worldwide. However, traditional indicators have limited predictive effects on the clinical outcomes of bladder cancer. The aim of this study was to develop and validate a glycolysis-related gene signature for predicting the prognos...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7238531/ https://www.ncbi.nlm.nih.gov/pubmed/32467671 http://dx.doi.org/10.1186/s12935-020-01255-2 |
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author | Zhang, Chen Gou, Xin He, Weiyang Yang, Huaan Yin, Hubin |
author_facet | Zhang, Chen Gou, Xin He, Weiyang Yang, Huaan Yin, Hubin |
author_sort | Zhang, Chen |
collection | PubMed |
description | BACKGROUND: Bladder cancer is one of the most prevalent malignancies worldwide. However, traditional indicators have limited predictive effects on the clinical outcomes of bladder cancer. The aim of this study was to develop and validate a glycolysis-related gene signature for predicting the prognosis of patients with bladder cancer that have limited therapeutic options. METHODS: mRNA expression profiling was obtained from patients with bladder cancer from The Cancer Genome Atlas (TCGA) database. Gene set enrichment analysis (GSEA) was conducted to identify glycolytic gene sets that were significantly different between bladder cancer tissues and paired normal tissues. A prognosis-related gene signature was constructed by univariate and multivariate Cox analysis. Kaplan–Meier curves and time-dependent receiver operating characteristic (ROC) curves were utilized to evaluate the signature. A nomogram combined with the gene signature and clinical parameters was constructed. Correlations between glycolysis-related gene signature and molecular characterization as well as cancer subtypes were analyzed. RT-qPCR was applied to analyze gene expression. Functional experiments were performed to determine the role of PKM2 in the proliferation of bladder cancer cells. RESULTS: Using a Cox proportional regression model, we established that a 4-mRNA signature (NUP205, NUPL2, PFKFB1 and PKM) was significantly associated with prognosis in bladder cancer patients. Based on the signature, patients were split into high and low risk groups, with different prognostic outcomes. The gene signature was an independent prognostic indicator for overall survival. The ability of the 4-mRNA signature to make an accurate prognosis was tested in two other validation datasets. GSEA was performed to explore the 4-mRNA related canonical pathways and biological processes, such as the cell cycle, hypoxia, p53 pathway, and PI3K/AKT/mTOR pathway. A heatmap showing the correlation between risk score and cell cycle signature was generated. RT-qPCR revealed the genes that were differentially expressed between normal and cancer tissues. Experiments showed that PKM2 plays essential roles in cell proliferation and the cell cycle. CONCLUSION: The established 4‑mRNA signature may act as a promising model for generating accurate prognoses for patients with bladder cancer, but the specific biological mechanism needs further verification. |
format | Online Article Text |
id | pubmed-7238531 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-72385312020-05-27 A glycolysis-based 4-mRNA signature correlates with the prognosis and cell cycle process in patients with bladder cancer Zhang, Chen Gou, Xin He, Weiyang Yang, Huaan Yin, Hubin Cancer Cell Int Primary Research BACKGROUND: Bladder cancer is one of the most prevalent malignancies worldwide. However, traditional indicators have limited predictive effects on the clinical outcomes of bladder cancer. The aim of this study was to develop and validate a glycolysis-related gene signature for predicting the prognosis of patients with bladder cancer that have limited therapeutic options. METHODS: mRNA expression profiling was obtained from patients with bladder cancer from The Cancer Genome Atlas (TCGA) database. Gene set enrichment analysis (GSEA) was conducted to identify glycolytic gene sets that were significantly different between bladder cancer tissues and paired normal tissues. A prognosis-related gene signature was constructed by univariate and multivariate Cox analysis. Kaplan–Meier curves and time-dependent receiver operating characteristic (ROC) curves were utilized to evaluate the signature. A nomogram combined with the gene signature and clinical parameters was constructed. Correlations between glycolysis-related gene signature and molecular characterization as well as cancer subtypes were analyzed. RT-qPCR was applied to analyze gene expression. Functional experiments were performed to determine the role of PKM2 in the proliferation of bladder cancer cells. RESULTS: Using a Cox proportional regression model, we established that a 4-mRNA signature (NUP205, NUPL2, PFKFB1 and PKM) was significantly associated with prognosis in bladder cancer patients. Based on the signature, patients were split into high and low risk groups, with different prognostic outcomes. The gene signature was an independent prognostic indicator for overall survival. The ability of the 4-mRNA signature to make an accurate prognosis was tested in two other validation datasets. GSEA was performed to explore the 4-mRNA related canonical pathways and biological processes, such as the cell cycle, hypoxia, p53 pathway, and PI3K/AKT/mTOR pathway. A heatmap showing the correlation between risk score and cell cycle signature was generated. RT-qPCR revealed the genes that were differentially expressed between normal and cancer tissues. Experiments showed that PKM2 plays essential roles in cell proliferation and the cell cycle. CONCLUSION: The established 4‑mRNA signature may act as a promising model for generating accurate prognoses for patients with bladder cancer, but the specific biological mechanism needs further verification. BioMed Central 2020-05-20 /pmc/articles/PMC7238531/ /pubmed/32467671 http://dx.doi.org/10.1186/s12935-020-01255-2 Text en © The Author(s) 2020 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Primary Research Zhang, Chen Gou, Xin He, Weiyang Yang, Huaan Yin, Hubin A glycolysis-based 4-mRNA signature correlates with the prognosis and cell cycle process in patients with bladder cancer |
title | A glycolysis-based 4-mRNA signature correlates with the prognosis and cell cycle process in patients with bladder cancer |
title_full | A glycolysis-based 4-mRNA signature correlates with the prognosis and cell cycle process in patients with bladder cancer |
title_fullStr | A glycolysis-based 4-mRNA signature correlates with the prognosis and cell cycle process in patients with bladder cancer |
title_full_unstemmed | A glycolysis-based 4-mRNA signature correlates with the prognosis and cell cycle process in patients with bladder cancer |
title_short | A glycolysis-based 4-mRNA signature correlates with the prognosis and cell cycle process in patients with bladder cancer |
title_sort | glycolysis-based 4-mrna signature correlates with the prognosis and cell cycle process in patients with bladder cancer |
topic | Primary Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7238531/ https://www.ncbi.nlm.nih.gov/pubmed/32467671 http://dx.doi.org/10.1186/s12935-020-01255-2 |
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