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Integrative multiomics analysis identifies a metastasis-related gene signature and the potential oncogenic role of EZR in breast cancer

Distant metastasis is a major cause of increased mortality in breast cancer patients, but the mechanisms underlying breast cancer metastasis remain poorly understood. In this study, we aimed to identify a metastasis-related gene (MRG) signature for predicting progression in breast cancer. By screeni...

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Autores principales: XIAO, GUODONG, CHENG, FENG, YUAN, JING, LU, WEIPING, WANG, PEILI, FAN, HUIJIE
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Tech Science Press 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10208079/
https://www.ncbi.nlm.nih.gov/pubmed/37304008
http://dx.doi.org/10.32604/or.2022.026616
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author XIAO, GUODONG
CHENG, FENG
YUAN, JING
LU, WEIPING
WANG, PEILI
FAN, HUIJIE
author_facet XIAO, GUODONG
CHENG, FENG
YUAN, JING
LU, WEIPING
WANG, PEILI
FAN, HUIJIE
author_sort XIAO, GUODONG
collection PubMed
description Distant metastasis is a major cause of increased mortality in breast cancer patients, but the mechanisms underlying breast cancer metastasis remain poorly understood. In this study, we aimed to identify a metastasis-related gene (MRG) signature for predicting progression in breast cancer. By screening using three regression analysis methods, a 9-gene signature (NOTCH1, PTP4A3, MMP13, MACC1, EZR, NEDD9, PIK3CA, F2RL1 and CCR7) was constructed based on an MRG set in the BRCA cohort from TCGA. This signature exhibited strong robustness, and its generalizability was verified in the Metabric and GEO cohorts. Of the nine MRGs, EZR is an oncogenic gene with a well-documented role in cell adhesion and cell migration, but it has rarely been investigated in breast cancer. Based on a search of different databases, EZR was found to be significantly more highly expressed in both breast cancer cells and breast cancer tissue. EZR knockdown significantly inhibited cell proliferation, invasion, chemoresistance and EMT in breast cancer. Mechanistically, RhoA activation assays confirmed that EZR knockdown inhibited the activity of RhoA, Rac1 and Cdc42. In summary, we identified a nine-MRG signature that can be used as an efficient prognostic indicator for breast cancer patients, and owing to its involvement in regulating breast cancer metastasis, EZR might serve as a therapeutic target.
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spelling pubmed-102080792023-06-10 Integrative multiomics analysis identifies a metastasis-related gene signature and the potential oncogenic role of EZR in breast cancer XIAO, GUODONG CHENG, FENG YUAN, JING LU, WEIPING WANG, PEILI FAN, HUIJIE Oncol Res Article Distant metastasis is a major cause of increased mortality in breast cancer patients, but the mechanisms underlying breast cancer metastasis remain poorly understood. In this study, we aimed to identify a metastasis-related gene (MRG) signature for predicting progression in breast cancer. By screening using three regression analysis methods, a 9-gene signature (NOTCH1, PTP4A3, MMP13, MACC1, EZR, NEDD9, PIK3CA, F2RL1 and CCR7) was constructed based on an MRG set in the BRCA cohort from TCGA. This signature exhibited strong robustness, and its generalizability was verified in the Metabric and GEO cohorts. Of the nine MRGs, EZR is an oncogenic gene with a well-documented role in cell adhesion and cell migration, but it has rarely been investigated in breast cancer. Based on a search of different databases, EZR was found to be significantly more highly expressed in both breast cancer cells and breast cancer tissue. EZR knockdown significantly inhibited cell proliferation, invasion, chemoresistance and EMT in breast cancer. Mechanistically, RhoA activation assays confirmed that EZR knockdown inhibited the activity of RhoA, Rac1 and Cdc42. In summary, we identified a nine-MRG signature that can be used as an efficient prognostic indicator for breast cancer patients, and owing to its involvement in regulating breast cancer metastasis, EZR might serve as a therapeutic target. Tech Science Press 2022-12-06 /pmc/articles/PMC10208079/ /pubmed/37304008 http://dx.doi.org/10.32604/or.2022.026616 Text en © 2022 Xiao et al. https://creativecommons.org/licenses/by/4.0/This work is licensed under a Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Article
XIAO, GUODONG
CHENG, FENG
YUAN, JING
LU, WEIPING
WANG, PEILI
FAN, HUIJIE
Integrative multiomics analysis identifies a metastasis-related gene signature and the potential oncogenic role of EZR in breast cancer
title Integrative multiomics analysis identifies a metastasis-related gene signature and the potential oncogenic role of EZR in breast cancer
title_full Integrative multiomics analysis identifies a metastasis-related gene signature and the potential oncogenic role of EZR in breast cancer
title_fullStr Integrative multiomics analysis identifies a metastasis-related gene signature and the potential oncogenic role of EZR in breast cancer
title_full_unstemmed Integrative multiomics analysis identifies a metastasis-related gene signature and the potential oncogenic role of EZR in breast cancer
title_short Integrative multiomics analysis identifies a metastasis-related gene signature and the potential oncogenic role of EZR in breast cancer
title_sort integrative multiomics analysis identifies a metastasis-related gene signature and the potential oncogenic role of ezr in breast cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10208079/
https://www.ncbi.nlm.nih.gov/pubmed/37304008
http://dx.doi.org/10.32604/or.2022.026616
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