Protein co-expression networks identified from HOT lesions of ER+HER2–Ki-67high luminal breast carcinomas

Abstract Patients with estrogen receptor-positive/human epidermal growth factor receptor 2-negative/Ki-67-high (ER+HER2–Ki-67high) luminal breast cancer have a worse prognosis and do not respond to hormonal treatment and chemotherapy. This study sought to identify disease-related protein networks si...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Kimito Yamada, Toshihide Nishimura, Midori Wakiya, Eiichi Satoh, Tetsuya Fukuda, Keigo Amaya, Yasuhiko Bando, Hiroshi Hirano, Takashi Ishikawa
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/3846f737546a4c368ddfcb4d4d714ceb
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:3846f737546a4c368ddfcb4d4d714ceb
record_format	dspace
spelling	oai:doaj.org-article:3846f737546a4c368ddfcb4d4d714ceb2021-12-02T10:49:34ZProtein co-expression networks identified from HOT lesions of ER+HER2–Ki-67high luminal breast carcinomas10.1038/s41598-021-81509-92045-2322https://doaj.org/article/3846f737546a4c368ddfcb4d4d714ceb2021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-81509-9https://doaj.org/toc/2045-2322Abstract Patients with estrogen receptor-positive/human epidermal growth factor receptor 2-negative/Ki-67-high (ER+HER2–Ki-67high) luminal breast cancer have a worse prognosis and do not respond to hormonal treatment and chemotherapy. This study sought to identify disease-related protein networks significantly associated with this subtype, by assessing in-depth proteomes of 10 lesions of high and low Ki-67 values (HOT, five; COLD, five) microdissected from the five tumors. Weighted correlation network analysis screened by over-representative analysis identified the five modules significantly associated with the HOT lesions. Pathway enrichment analysis, together with causal network analysis, revealed pathways of ribosome-associated quality controls, heat shock response by oxidative stress and hypoxia, angiogenesis, and oxidative phosphorylation. A semi-quantitative correlation of key-protein expressions, protein co-regulation analysis, and multivariate correlation analysis suggested co-regulations via network-network interaction among the four HOT-characteristic modules. Predicted highly activated master and upstream regulators were most characteristic to ER-positive breast cancer and associated with oncogenic transformation, as well as resistance to chemotherapy and endocrine therapy. Interestingly, inhibited intervention causal networks of numerous chemical inhibitors were predicted within the top 10 lists for the WM2 and WM5 modules, suggesting involvement of potential therapeutic targets in those data-driven networks. Our findings may help develop therapeutic strategies to benefit patients.Kimito YamadaToshihide NishimuraMidori WakiyaEiichi SatohTetsuya FukudaKeigo AmayaYasuhiko BandoHiroshi HiranoTakashi IshikawaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Kimito Yamada Toshihide Nishimura Midori Wakiya Eiichi Satoh Tetsuya Fukuda Keigo Amaya Yasuhiko Bando Hiroshi Hirano Takashi Ishikawa Protein co-expression networks identified from HOT lesions of ER+HER2–Ki-67high luminal breast carcinomas
description	Abstract Patients with estrogen receptor-positive/human epidermal growth factor receptor 2-negative/Ki-67-high (ER+HER2–Ki-67high) luminal breast cancer have a worse prognosis and do not respond to hormonal treatment and chemotherapy. This study sought to identify disease-related protein networks significantly associated with this subtype, by assessing in-depth proteomes of 10 lesions of high and low Ki-67 values (HOT, five; COLD, five) microdissected from the five tumors. Weighted correlation network analysis screened by over-representative analysis identified the five modules significantly associated with the HOT lesions. Pathway enrichment analysis, together with causal network analysis, revealed pathways of ribosome-associated quality controls, heat shock response by oxidative stress and hypoxia, angiogenesis, and oxidative phosphorylation. A semi-quantitative correlation of key-protein expressions, protein co-regulation analysis, and multivariate correlation analysis suggested co-regulations via network-network interaction among the four HOT-characteristic modules. Predicted highly activated master and upstream regulators were most characteristic to ER-positive breast cancer and associated with oncogenic transformation, as well as resistance to chemotherapy and endocrine therapy. Interestingly, inhibited intervention causal networks of numerous chemical inhibitors were predicted within the top 10 lists for the WM2 and WM5 modules, suggesting involvement of potential therapeutic targets in those data-driven networks. Our findings may help develop therapeutic strategies to benefit patients.
format	article
author	Kimito Yamada Toshihide Nishimura Midori Wakiya Eiichi Satoh Tetsuya Fukuda Keigo Amaya Yasuhiko Bando Hiroshi Hirano Takashi Ishikawa
author_facet	Kimito Yamada Toshihide Nishimura Midori Wakiya Eiichi Satoh Tetsuya Fukuda Keigo Amaya Yasuhiko Bando Hiroshi Hirano Takashi Ishikawa
author_sort	Kimito Yamada
title	Protein co-expression networks identified from HOT lesions of ER+HER2–Ki-67high luminal breast carcinomas
title_short	Protein co-expression networks identified from HOT lesions of ER+HER2–Ki-67high luminal breast carcinomas
title_full	Protein co-expression networks identified from HOT lesions of ER+HER2–Ki-67high luminal breast carcinomas
title_fullStr	Protein co-expression networks identified from HOT lesions of ER+HER2–Ki-67high luminal breast carcinomas
title_full_unstemmed	Protein co-expression networks identified from HOT lesions of ER+HER2–Ki-67high luminal breast carcinomas
title_sort	protein co-expression networks identified from hot lesions of er+her2–ki-67high luminal breast carcinomas
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/3846f737546a4c368ddfcb4d4d714ceb
work_keys_str_mv	AT kimitoyamada proteincoexpressionnetworksidentifiedfromhotlesionsoferher2ki67highluminalbreastcarcinomas AT toshihidenishimura proteincoexpressionnetworksidentifiedfromhotlesionsoferher2ki67highluminalbreastcarcinomas AT midoriwakiya proteincoexpressionnetworksidentifiedfromhotlesionsoferher2ki67highluminalbreastcarcinomas AT eiichisatoh proteincoexpressionnetworksidentifiedfromhotlesionsoferher2ki67highluminalbreastcarcinomas AT tetsuyafukuda proteincoexpressionnetworksidentifiedfromhotlesionsoferher2ki67highluminalbreastcarcinomas AT keigoamaya proteincoexpressionnetworksidentifiedfromhotlesionsoferher2ki67highluminalbreastcarcinomas AT yasuhikobando proteincoexpressionnetworksidentifiedfromhotlesionsoferher2ki67highluminalbreastcarcinomas AT hiroshihirano proteincoexpressionnetworksidentifiedfromhotlesionsoferher2ki67highluminalbreastcarcinomas AT takashiishikawa proteincoexpressionnetworksidentifiedfromhotlesionsoferher2ki67highluminalbreastcarcinomas
_version_	1718396582940901376

Protein co-expression networks identified from HOT lesions of ER+HER2–Ki-67high luminal breast carcinomas

Ejemplares similares