Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Li, Juanni, Hu, Kuan, Zhou, Lei, Huang, Jinzhou, Zeng, Shuangshuang, Xu, Zhijie, Yan, Yuanliang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
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
_version_ 1783601456533733376
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
work_keys_str_mv AT lijuanni spectrumofmesenchymalepithelialtransitionaberrationsandpotentialclinicalimplicationsinsightsfromintegrativepancanceranalysis
AT hukuan spectrumofmesenchymalepithelialtransitionaberrationsandpotentialclinicalimplicationsinsightsfromintegrativepancanceranalysis
AT zhoulei spectrumofmesenchymalepithelialtransitionaberrationsandpotentialclinicalimplicationsinsightsfromintegrativepancanceranalysis
AT huangjinzhou spectrumofmesenchymalepithelialtransitionaberrationsandpotentialclinicalimplicationsinsightsfromintegrativepancanceranalysis
AT zengshuangshuang spectrumofmesenchymalepithelialtransitionaberrationsandpotentialclinicalimplicationsinsightsfromintegrativepancanceranalysis
AT xuzhijie spectrumofmesenchymalepithelialtransitionaberrationsandpotentialclinicalimplicationsinsightsfromintegrativepancanceranalysis
AT yanyuanliang spectrumofmesenchymalepithelialtransitionaberrationsandpotentialclinicalimplicationsinsightsfromintegrativepancanceranalysis