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Integrative analysis of prognostic value and immune infiltration of spindle and kinetochore-associated family members in breast cancer. | LitMetric

AI Article Synopsis

  • The SKA complex (SKA1, SKA2, SKA3) is linked to the stability of mitotic metaphase and may play a role in cancer regulation, particularly in breast cancer (BC), although its specific functions are not fully understood.
  • Analysis of databases revealed that SKA1, SKA2, and SKA3 are all overexpressed in BC, with SKA3's overexpression associated with poor survival outcomes, while SKA1 shows potential as a good prognostic marker in HER2-positive BC.
  • The study found that SKA expression negatively correlates with immune cell infiltration and positively correlates with immune checkpoint molecules, and silencing these genes inhibits BC cell growth and movement, suggesting

Article Abstract

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.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8809973PMC
http://dx.doi.org/10.1080/21655979.2021.1995576DOI Listing

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