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An integrated autophagy-related gene signature predicts prognosis in human endometrial Cancer
BACKGROUND: Globally, endometrial cancer is the fourth most common malignant tumor in women and the number of women being diagnosed is increasing. Tumor progression is strongly related to the cell survival-promoting functions of autophagy. We explored the relationship between endometrial cancer prog...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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BioMed Central
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7590615/ https://www.ncbi.nlm.nih.gov/pubmed/33109128 http://dx.doi.org/10.1186/s12885-020-07535-4 |
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author | Zhang, Jun Wang, Ziwei Zhao, Rong An, Lanfen Zhou, Xing Zhao, Yingchao Wang, Hongbo |
author_facet | Zhang, Jun Wang, Ziwei Zhao, Rong An, Lanfen Zhou, Xing Zhao, Yingchao Wang, Hongbo |
author_sort | Zhang, Jun |
collection | PubMed |
description | BACKGROUND: Globally, endometrial cancer is the fourth most common malignant tumor in women and the number of women being diagnosed is increasing. Tumor progression is strongly related to the cell survival-promoting functions of autophagy. We explored the relationship between endometrial cancer prognoses and the expression of autophagy genes using human autophagy databases. METHODS: The Cancer Genome Atlas was used to identify autophagy related genes (ARGs) that were differentially expressed in endometrial cancer tissue compared to healthy endometrial tissue. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes were referenced to identify important biological functions and signaling pathways related to these differentially expressed ARGs. A prognostic model for endometrial cancer was constructed using univariate and multivariate Cox, and Least Absolute Shrinkage and Selection Operator regression analysis. Endometrial cancer patients were divided into high- and low-risk groups according to risk scores. Survival and receiver operating characteristic (ROC) curves were plotted for these patients to assess the accuracy of the prognostic model. Using immunohistochemistry the protein levels of the genes associated with risk were assessed. RESULTS: We determined 37 ARGs were differentially expressed between endometrial cancer and healthy tissues. These genes were enriched in the biological processes and signaling pathways related to autophagy. Four ARGs (CDKN2A, PTK6, ERBB2 and BIRC5) were selected to establish a prognostic model of endometrial cancer. Kaplan–Meier survival analysis suggested that high-risk groups have significantly shorter survival times than low-risk groups. The area under the ROC curve indicated that the prognostic model for survival prediction was relatively accurate. Immunohistochemistry suggested that among the four ARGs the protein levels of CDKN2A, PTK6, ERBB2, and BIRC5 were higher in endometrial cancer than healthy endometrial tissue. CONCLUSIONS: Our prognostic model assessing four ARGs (CDKN2A, PTK6, ERBB2, and BIRC5) suggested their potential as independent predictive biomarkers and therapeutic targets for endometrial cancer. SUPPLEMENTARY INFORMATION: Supplementary information accompanies this paper at 10.1186/s12885-020-07535-4. |
format | Online Article Text |
id | pubmed-7590615 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-75906152020-10-27 An integrated autophagy-related gene signature predicts prognosis in human endometrial Cancer Zhang, Jun Wang, Ziwei Zhao, Rong An, Lanfen Zhou, Xing Zhao, Yingchao Wang, Hongbo BMC Cancer Research Article BACKGROUND: Globally, endometrial cancer is the fourth most common malignant tumor in women and the number of women being diagnosed is increasing. Tumor progression is strongly related to the cell survival-promoting functions of autophagy. We explored the relationship between endometrial cancer prognoses and the expression of autophagy genes using human autophagy databases. METHODS: The Cancer Genome Atlas was used to identify autophagy related genes (ARGs) that were differentially expressed in endometrial cancer tissue compared to healthy endometrial tissue. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes were referenced to identify important biological functions and signaling pathways related to these differentially expressed ARGs. A prognostic model for endometrial cancer was constructed using univariate and multivariate Cox, and Least Absolute Shrinkage and Selection Operator regression analysis. Endometrial cancer patients were divided into high- and low-risk groups according to risk scores. Survival and receiver operating characteristic (ROC) curves were plotted for these patients to assess the accuracy of the prognostic model. Using immunohistochemistry the protein levels of the genes associated with risk were assessed. RESULTS: We determined 37 ARGs were differentially expressed between endometrial cancer and healthy tissues. These genes were enriched in the biological processes and signaling pathways related to autophagy. Four ARGs (CDKN2A, PTK6, ERBB2 and BIRC5) were selected to establish a prognostic model of endometrial cancer. Kaplan–Meier survival analysis suggested that high-risk groups have significantly shorter survival times than low-risk groups. The area under the ROC curve indicated that the prognostic model for survival prediction was relatively accurate. Immunohistochemistry suggested that among the four ARGs the protein levels of CDKN2A, PTK6, ERBB2, and BIRC5 were higher in endometrial cancer than healthy endometrial tissue. CONCLUSIONS: Our prognostic model assessing four ARGs (CDKN2A, PTK6, ERBB2, and BIRC5) suggested their potential as independent predictive biomarkers and therapeutic targets for endometrial cancer. SUPPLEMENTARY INFORMATION: Supplementary information accompanies this paper at 10.1186/s12885-020-07535-4. BioMed Central 2020-10-27 /pmc/articles/PMC7590615/ /pubmed/33109128 http://dx.doi.org/10.1186/s12885-020-07535-4 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 | Research Article Zhang, Jun Wang, Ziwei Zhao, Rong An, Lanfen Zhou, Xing Zhao, Yingchao Wang, Hongbo An integrated autophagy-related gene signature predicts prognosis in human endometrial Cancer |
title | An integrated autophagy-related gene signature predicts prognosis in human endometrial Cancer |
title_full | An integrated autophagy-related gene signature predicts prognosis in human endometrial Cancer |
title_fullStr | An integrated autophagy-related gene signature predicts prognosis in human endometrial Cancer |
title_full_unstemmed | An integrated autophagy-related gene signature predicts prognosis in human endometrial Cancer |
title_short | An integrated autophagy-related gene signature predicts prognosis in human endometrial Cancer |
title_sort | integrated autophagy-related gene signature predicts prognosis in human endometrial cancer |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7590615/ https://www.ncbi.nlm.nih.gov/pubmed/33109128 http://dx.doi.org/10.1186/s12885-020-07535-4 |
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