Expression pattern and prognostic impact of glycoprotein non-metastatic B (GPNMB) in triple-negative breast cancer

Abstract Glycoprotein non-metastatic B (GPNMB) is a transmembrane protein overexpressed in numerous cancers including triple-negative breast cancers (TNBC). It has been linked to promote cancer aggressiveness and implicated as a novel target for GPNMB-expressing cancers. In current study, we aimed t...

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Autores principales:	Yu-Hsiang Huang, Pei-Yi Chu, Ji-Lin Chen, Chun-Teng Huang, Chi-Cheng Huang, Yi‐Fang Tsai, Yu-Ling Wang, Pei-Ju Lien, Ling-Ming Tseng, Chun-Yu Liu
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/43b1134988854ea293e0ee0cce3ecc5e
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spelling	oai:doaj.org-article:43b1134988854ea293e0ee0cce3ecc5e2021-12-02T17:30:34ZExpression pattern and prognostic impact of glycoprotein non-metastatic B (GPNMB) in triple-negative breast cancer10.1038/s41598-021-91588-32045-2322https://doaj.org/article/43b1134988854ea293e0ee0cce3ecc5e2021-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-91588-3https://doaj.org/toc/2045-2322Abstract Glycoprotein non-metastatic B (GPNMB) is a transmembrane protein overexpressed in numerous cancers including triple-negative breast cancers (TNBC). It has been linked to promote cancer aggressiveness and implicated as a novel target for GPNMB-expressing cancers. In current study, we aimed to explore the clinical significance of GPNMB in TNBC. Among 759 specimens, immunohistochemistry (IHC) exhibited GPNMB expressions were variable in different subtypes and significantly higher in TNBC. Kaplan–Meier analysis revealed GPNMB overexpression in TNBC was associated with worse prognosis especially distant metastasis (P = 0.020, HR = 2.515, CI 1.154–5.480). Multivariate analysis showed GPNMB expression was an independent prognostic factor in terms of recurrence and distant metastasis (P = 0.008, HR = 3.22, CI 1.36–7.61; P = 0.017, HR = 3.08, CI 1.22–7.74). In silico analysis showed high mRNA expression of GPNMB was associated with distant metastasis and GPNMB was overexpressed in TNBC. Furthermore, GPNMB positively correlated with epithelial–mesenchymal transition (EMT) regulators, mesenchymal marker vimentin, MMP and integrins. The protein levels of Twist and MMP2 were upregulated by GPNMB overexpression in TNBC cells. GPNMB-enhanced cell invasion was attenuated by broad spectrum MMP inhibitor (GM 6001) and the selective inhibitor of MMP-2 (ARP100). In summary, GPNMB expression is prevalent in TNBC and may be implicated as a prognostic biomarker in patients with TNBC.Yu-Hsiang HuangPei-Yi ChuJi-Lin ChenChun-Teng HuangChi-Cheng HuangYi‐Fang TsaiYu-Ling WangPei-Ju LienLing-Ming TsengChun-Yu LiuNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Yu-Hsiang Huang Pei-Yi Chu Ji-Lin Chen Chun-Teng Huang Chi-Cheng Huang Yi‐Fang Tsai Yu-Ling Wang Pei-Ju Lien Ling-Ming Tseng Chun-Yu Liu Expression pattern and prognostic impact of glycoprotein non-metastatic B (GPNMB) in triple-negative breast cancer
description	Abstract Glycoprotein non-metastatic B (GPNMB) is a transmembrane protein overexpressed in numerous cancers including triple-negative breast cancers (TNBC). It has been linked to promote cancer aggressiveness and implicated as a novel target for GPNMB-expressing cancers. In current study, we aimed to explore the clinical significance of GPNMB in TNBC. Among 759 specimens, immunohistochemistry (IHC) exhibited GPNMB expressions were variable in different subtypes and significantly higher in TNBC. Kaplan–Meier analysis revealed GPNMB overexpression in TNBC was associated with worse prognosis especially distant metastasis (P = 0.020, HR = 2.515, CI 1.154–5.480). Multivariate analysis showed GPNMB expression was an independent prognostic factor in terms of recurrence and distant metastasis (P = 0.008, HR = 3.22, CI 1.36–7.61; P = 0.017, HR = 3.08, CI 1.22–7.74). In silico analysis showed high mRNA expression of GPNMB was associated with distant metastasis and GPNMB was overexpressed in TNBC. Furthermore, GPNMB positively correlated with epithelial–mesenchymal transition (EMT) regulators, mesenchymal marker vimentin, MMP and integrins. The protein levels of Twist and MMP2 were upregulated by GPNMB overexpression in TNBC cells. GPNMB-enhanced cell invasion was attenuated by broad spectrum MMP inhibitor (GM 6001) and the selective inhibitor of MMP-2 (ARP100). In summary, GPNMB expression is prevalent in TNBC and may be implicated as a prognostic biomarker in patients with TNBC.
format	article
author	Yu-Hsiang Huang Pei-Yi Chu Ji-Lin Chen Chun-Teng Huang Chi-Cheng Huang Yi‐Fang Tsai Yu-Ling Wang Pei-Ju Lien Ling-Ming Tseng Chun-Yu Liu
author_facet	Yu-Hsiang Huang Pei-Yi Chu Ji-Lin Chen Chun-Teng Huang Chi-Cheng Huang Yi‐Fang Tsai Yu-Ling Wang Pei-Ju Lien Ling-Ming Tseng Chun-Yu Liu
author_sort	Yu-Hsiang Huang
title	Expression pattern and prognostic impact of glycoprotein non-metastatic B (GPNMB) in triple-negative breast cancer
title_short	Expression pattern and prognostic impact of glycoprotein non-metastatic B (GPNMB) in triple-negative breast cancer
title_full	Expression pattern and prognostic impact of glycoprotein non-metastatic B (GPNMB) in triple-negative breast cancer
title_fullStr	Expression pattern and prognostic impact of glycoprotein non-metastatic B (GPNMB) in triple-negative breast cancer
title_full_unstemmed	Expression pattern and prognostic impact of glycoprotein non-metastatic B (GPNMB) in triple-negative breast cancer
title_sort	expression pattern and prognostic impact of glycoprotein non-metastatic b (gpnmb) in triple-negative breast cancer
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/43b1134988854ea293e0ee0cce3ecc5e
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Expression pattern and prognostic impact of glycoprotein non-metastatic B (GPNMB) in triple-negative breast cancer

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