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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| Format: | Article |
| Language: | English |
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Nature Portfolio
2021-06-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-021-91588-3 |
| _version_ | 1831706242494496768 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-20T16:34:30Z |
| format | Article |
| id | doaj.art-43b1134988854ea293e0ee0cce3ecc5e |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-20T16:34:30Z |
| publishDate | 2021-06-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-43b1134988854ea293e0ee0cce3ecc5e2022-12-21T19:33:10ZengNature PortfolioScientific Reports2045-23222021-06-0111111210.1038/s41598-021-91588-3Expression pattern and prognostic impact of glycoprotein non-metastatic B (GPNMB) in triple-negative breast cancerYu-Hsiang Huang0Pei-Yi Chu1Ji-Lin Chen2Chun-Teng Huang3Chi-Cheng Huang4Yi‐Fang Tsai5Yu-Ling Wang6Pei-Ju Lien7Ling-Ming Tseng8Chun-Yu Liu9School of Medicine, National Yang Ming Chiao Tung UniversityDepartment of Pathology, Show Chwan Memorial HospitalComprehensive Breast Health Center, Taipei Veterans General HospitalSchool of Medicine, National Yang Ming Chiao Tung UniversityComprehensive Breast Health Center, Taipei Veterans General HospitalSchool of Medicine, National Yang Ming Chiao Tung UniversityComprehensive Breast Health Center, Taipei Veterans General HospitalComprehensive Breast Health Center, Taipei Veterans General HospitalSchool of Medicine, National Yang Ming Chiao Tung UniversitySchool of Medicine, National Yang Ming Chiao Tung UniversityAbstract 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.https://doi.org/10.1038/s41598-021-91588-3 |
| spellingShingle | 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 Scientific Reports |
| title | 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_short | 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 |
| url | https://doi.org/10.1038/s41598-021-91588-3 |
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