Integrative analysis of prognostic value and immune infiltration of spindle and kinetochore-associated family members in breast cancer
Spindle and kinetochore associated (SKA) complex subunit, which maintains the stability of mitotic metaphase, with emerging research implying its effect as a carcinogenic regulator in cancer. However, its potential role in BC has not been fully elucidated. ONCOMINE, UALCAN, GEPIA, Kaplan-Meier Plott...
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2021
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oai:doaj.org-article:16a7d07713d24e1ab95235add8b043602021-12-01T14:41:00ZIntegrative analysis of prognostic value and immune infiltration of spindle and kinetochore-associated family members in breast cancer2165-59792165-598710.1080/21655979.2021.1995576https://doaj.org/article/16a7d07713d24e1ab95235add8b043602021-12-01T00:00:00Zhttp://dx.doi.org/10.1080/21655979.2021.1995576https://doaj.org/toc/2165-5979https://doaj.org/toc/2165-5987Spindle and kinetochore associated (SKA) complex subunit, which maintains the stability of mitotic metaphase, with emerging research implying its effect as a carcinogenic regulator in cancer. However, its potential role in BC has not been fully elucidated. ONCOMINE, UALCAN, GEPIA, Kaplan-Meier Plotter, cBioPortal and TIMER databases were performed to analyze the expression, prognosis, mutation, immune infiltration and potential biological mechanisms of SKA1/2/3 in BC. Our results showed that SKA1/2/3 expression was upregulated in BC. Survival analysis reveals that SKA3 overexpression was associated with poor overall survival (OS), relapse-free survival (RFS), post-progression survival (PPS) and distant metastasis-free survival (DMFS). SKA1 overexpression was associated with poor OS, RFS and DMFS while SKA2 overexpression was only associated with RFS and DMFS. Notably, the results implied that SKA1 has a good prognostic value in HER2-positive BC. Besides, the genetic alterations of SKA were investigated and the altered group correlated with shorter progress-free survival (PFS) and disease-specific survival (DSS). GO and KEGG analysis showed that SKA1/2/3 were implicated in regulating cell cycle, p53 signaling pathway and DNA replication. The 10 Hub genes in the protein network were upregulated in BC and related to poorer prognosis. Additionally, SKA1/2/3 expression was negatively correlated with infiltration of various immune cells with antitumor effects, whereas positively correlated with the expression of immune checkpoints molecules. Further experiments revealed that SKA1/2/3 silencing markedly impeded the proliferation and migration of BC cells. Herein, our study firmly shows that SKA genes may serve as a promising therapeutic target for patients with BC.Jianfeng DingXiaobo HeJinkun WangGuodong CaoSihan ChenLiping YuanBo ChenMaoming XiongTaylor & Francis Grouparticlespindle and kinetochore associated complex subunitbreast cancerprognosisimmune infiltratesbiomarkerBiotechnologyTP248.13-248.65ENBioengineered, Vol 12, Iss 2, Pp 10905-10923 (2021) |
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spindle and kinetochore associated complex subunit breast cancer prognosis immune infiltrates biomarker Biotechnology TP248.13-248.65 |
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spindle and kinetochore associated complex subunit breast cancer prognosis immune infiltrates biomarker Biotechnology TP248.13-248.65 Jianfeng Ding Xiaobo He Jinkun Wang Guodong Cao Sihan Chen Liping Yuan Bo Chen Maoming Xiong Integrative analysis of prognostic value and immune infiltration of spindle and kinetochore-associated family members in breast cancer |
description |
Spindle and kinetochore associated (SKA) complex subunit, which maintains the stability of mitotic metaphase, with emerging research implying its effect as a carcinogenic regulator in cancer. However, its potential role in BC has not been fully elucidated. ONCOMINE, UALCAN, GEPIA, Kaplan-Meier Plotter, cBioPortal and TIMER databases were performed to analyze the expression, prognosis, mutation, immune infiltration and potential biological mechanisms of SKA1/2/3 in BC. Our results showed that SKA1/2/3 expression was upregulated in BC. Survival analysis reveals that SKA3 overexpression was associated with poor overall survival (OS), relapse-free survival (RFS), post-progression survival (PPS) and distant metastasis-free survival (DMFS). SKA1 overexpression was associated with poor OS, RFS and DMFS while SKA2 overexpression was only associated with RFS and DMFS. Notably, the results implied that SKA1 has a good prognostic value in HER2-positive BC. Besides, the genetic alterations of SKA were investigated and the altered group correlated with shorter progress-free survival (PFS) and disease-specific survival (DSS). GO and KEGG analysis showed that SKA1/2/3 were implicated in regulating cell cycle, p53 signaling pathway and DNA replication. The 10 Hub genes in the protein network were upregulated in BC and related to poorer prognosis. Additionally, SKA1/2/3 expression was negatively correlated with infiltration of various immune cells with antitumor effects, whereas positively correlated with the expression of immune checkpoints molecules. Further experiments revealed that SKA1/2/3 silencing markedly impeded the proliferation and migration of BC cells. Herein, our study firmly shows that SKA genes may serve as a promising therapeutic target for patients with BC. |
format |
article |
author |
Jianfeng Ding Xiaobo He Jinkun Wang Guodong Cao Sihan Chen Liping Yuan Bo Chen Maoming Xiong |
author_facet |
Jianfeng Ding Xiaobo He Jinkun Wang Guodong Cao Sihan Chen Liping Yuan Bo Chen Maoming Xiong |
author_sort |
Jianfeng Ding |
title |
Integrative analysis of prognostic value and immune infiltration of spindle and kinetochore-associated family members in breast cancer |
title_short |
Integrative analysis of prognostic value and immune infiltration of spindle and kinetochore-associated family members in breast cancer |
title_full |
Integrative analysis of prognostic value and immune infiltration of spindle and kinetochore-associated family members in breast cancer |
title_fullStr |
Integrative analysis of prognostic value and immune infiltration of spindle and kinetochore-associated family members in breast cancer |
title_full_unstemmed |
Integrative analysis of prognostic value and immune infiltration of spindle and kinetochore-associated family members in breast cancer |
title_sort |
integrative analysis of prognostic value and immune infiltration of spindle and kinetochore-associated family members in breast cancer |
publisher |
Taylor & Francis Group |
publishDate |
2021 |
url |
https://doaj.org/article/16a7d07713d24e1ab95235add8b04360 |
work_keys_str_mv |
AT jianfengding integrativeanalysisofprognosticvalueandimmuneinfiltrationofspindleandkinetochoreassociatedfamilymembersinbreastcancer AT xiaobohe integrativeanalysisofprognosticvalueandimmuneinfiltrationofspindleandkinetochoreassociatedfamilymembersinbreastcancer AT jinkunwang integrativeanalysisofprognosticvalueandimmuneinfiltrationofspindleandkinetochoreassociatedfamilymembersinbreastcancer AT guodongcao integrativeanalysisofprognosticvalueandimmuneinfiltrationofspindleandkinetochoreassociatedfamilymembersinbreastcancer AT sihanchen integrativeanalysisofprognosticvalueandimmuneinfiltrationofspindleandkinetochoreassociatedfamilymembersinbreastcancer AT lipingyuan integrativeanalysisofprognosticvalueandimmuneinfiltrationofspindleandkinetochoreassociatedfamilymembersinbreastcancer AT bochen integrativeanalysisofprognosticvalueandimmuneinfiltrationofspindleandkinetochoreassociatedfamilymembersinbreastcancer AT maomingxiong integrativeanalysisofprognosticvalueandimmuneinfiltrationofspindleandkinetochoreassociatedfamilymembersinbreastcancer |
_version_ |
1718404978818678784 |