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Spectrum of Mesenchymal–Epithelial Transition Aberrations and Potential Clinical Implications: Insights From Integrative Pancancer Analysis
BACKGROUND: The receptor tyrosine kinase mesenchymal–epithelial transition factor (MET) is frequently altered in cancers and is a common therapeutic target for cancers with MET variants. However, abnormal MET alterations and their associations with patient outcome across different cancer types have...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7593712/ https://www.ncbi.nlm.nih.gov/pubmed/33178590 http://dx.doi.org/10.3389/fonc.2020.560615 |
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author | Li, Juanni Hu, Kuan Zhou, Lei Huang, Jinzhou Zeng, Shuangshuang Xu, Zhijie Yan, Yuanliang |
author_facet | Li, Juanni Hu, Kuan Zhou, Lei Huang, Jinzhou Zeng, Shuangshuang Xu, Zhijie Yan, Yuanliang |
author_sort | Li, Juanni |
collection | PubMed |
description | BACKGROUND: The receptor tyrosine kinase mesenchymal–epithelial transition factor (MET) is frequently altered in cancers and is a common therapeutic target for cancers with MET variants. However, abnormal MET alterations and their associations with patient outcome across different cancer types have not been studied simultaneously. In this study, we try to fill the vacancy in a comprehensive manner and capture the full MET alteration spectrum. METHODS: A total of 10,967 tumor samples comprising 32 cancer types from The Cancer Genome Atlas (TCGA) datasets were analyzed for MET abnormal expression, mutations, and copy number variants (CNVs). RESULTS: MET abnormal expression, alteration frequency, mutation site distribution, and functional impact varied across different cancer types. Lung adenocarcinoma (LUAD) has most targetable mutations located in the juxtamembrane domain, and both high expression and amplification of MET are significantly associated with poor prognosis. Kidney renal papillary cell carcinoma (KIRP) harbored the third highest alteration frequency of MET, which was dominated by mutations. While most mutations were in the Pkinase_Tyr domain, a few were targetable. Pancreatic adenocarcinoma (PAAD) harbors very few alterations, but increased MET expression is associated with poor outcomes. Esophageal carcinoma (ESCA), stomach adenocarcinoma (STAD), and ovarian serous cystadenocarcinoma (OV) had similar characteristics: a high frequency of MET CNVs but relatively few MET mutations, and high MET expression associated with poor prognosis. CONCLUSION: This study provided significant and comprehensive information regarding MET abnormal expression, alterations (mutations and CNVs), and their clinical associations among 32 cancer types and offered insights into the full MET alteration spectrum and its implications for prognosis and treatment. |
format | Online Article Text |
id | pubmed-7593712 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-75937122020-11-10 Spectrum of Mesenchymal–Epithelial Transition Aberrations and Potential Clinical Implications: Insights From Integrative Pancancer Analysis Li, Juanni Hu, Kuan Zhou, Lei Huang, Jinzhou Zeng, Shuangshuang Xu, Zhijie Yan, Yuanliang Front Oncol Oncology BACKGROUND: The receptor tyrosine kinase mesenchymal–epithelial transition factor (MET) is frequently altered in cancers and is a common therapeutic target for cancers with MET variants. However, abnormal MET alterations and their associations with patient outcome across different cancer types have not been studied simultaneously. In this study, we try to fill the vacancy in a comprehensive manner and capture the full MET alteration spectrum. METHODS: A total of 10,967 tumor samples comprising 32 cancer types from The Cancer Genome Atlas (TCGA) datasets were analyzed for MET abnormal expression, mutations, and copy number variants (CNVs). RESULTS: MET abnormal expression, alteration frequency, mutation site distribution, and functional impact varied across different cancer types. Lung adenocarcinoma (LUAD) has most targetable mutations located in the juxtamembrane domain, and both high expression and amplification of MET are significantly associated with poor prognosis. Kidney renal papillary cell carcinoma (KIRP) harbored the third highest alteration frequency of MET, which was dominated by mutations. While most mutations were in the Pkinase_Tyr domain, a few were targetable. Pancreatic adenocarcinoma (PAAD) harbors very few alterations, but increased MET expression is associated with poor outcomes. Esophageal carcinoma (ESCA), stomach adenocarcinoma (STAD), and ovarian serous cystadenocarcinoma (OV) had similar characteristics: a high frequency of MET CNVs but relatively few MET mutations, and high MET expression associated with poor prognosis. CONCLUSION: This study provided significant and comprehensive information regarding MET abnormal expression, alterations (mutations and CNVs), and their clinical associations among 32 cancer types and offered insights into the full MET alteration spectrum and its implications for prognosis and treatment. Frontiers Media S.A. 2020-10-15 /pmc/articles/PMC7593712/ /pubmed/33178590 http://dx.doi.org/10.3389/fonc.2020.560615 Text en Copyright © 2020 Li, Hu, Zhou, Huang, Zeng, Xu and Yan. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Oncology Li, Juanni Hu, Kuan Zhou, Lei Huang, Jinzhou Zeng, Shuangshuang Xu, Zhijie Yan, Yuanliang Spectrum of Mesenchymal–Epithelial Transition Aberrations and Potential Clinical Implications: Insights From Integrative Pancancer Analysis |
title | Spectrum of Mesenchymal–Epithelial Transition Aberrations and Potential Clinical Implications: Insights From Integrative Pancancer Analysis |
title_full | Spectrum of Mesenchymal–Epithelial Transition Aberrations and Potential Clinical Implications: Insights From Integrative Pancancer Analysis |
title_fullStr | Spectrum of Mesenchymal–Epithelial Transition Aberrations and Potential Clinical Implications: Insights From Integrative Pancancer Analysis |
title_full_unstemmed | Spectrum of Mesenchymal–Epithelial Transition Aberrations and Potential Clinical Implications: Insights From Integrative Pancancer Analysis |
title_short | Spectrum of Mesenchymal–Epithelial Transition Aberrations and Potential Clinical Implications: Insights From Integrative Pancancer Analysis |
title_sort | spectrum of mesenchymal–epithelial transition aberrations and potential clinical implications: insights from integrative pancancer analysis |
topic | Oncology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7593712/ https://www.ncbi.nlm.nih.gov/pubmed/33178590 http://dx.doi.org/10.3389/fonc.2020.560615 |
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