Overexpression of SKA3 correlates with poor prognosis in female early breast cancer

Abstract

Background Spindle and kinetochore associated complex subunit 3 (SKA3) plays an important role in tumorigenesis and the progression of various tumors. But the relationship between SKA3 and early breast cancer remains unclear. The study aimed to explore the prognostic significance of SKA3 in breast cancer. Methods In the study, SKA3 expression was initially assessed using the Oncomine database and The Cancer Genome Atlas database (TCGA). Then, we presented validation results for RT-qPCR (quantitative reverse transcription PCR) and ELISA (enzyme-linked immunosorbent assay). The relationship between clinical characteristics and SKA3 expression was assessed by Chi-square test and Fisher’s exact test. Kaplan–Meier method and Cox regression analysis were conducted to evaluate the prognostic value of SKA3. Gene set enrichment analysis (GSEA) was performed to screen biological pathways using the TCGA dataset. Besides, single sample gene set enrichment analysis (ssGSEA) was utilized to identify immune infiltration cells about SKA3. Results SKA3 mRNA was expressed at high levels in breast cancer tissues compared with normal tissues. Chi-square test and Fisher’s exact test showed SKA3 expression was related to age, tumor (T) classification, node (N) classification, tumor-node-metastasis (TNM) stage, estrogen receptor (ER), progesterone receptor (PR), molecular subtype, and race. RT-qPCR results showed that SKA3 expression was overexpressed in ER, PR status, and molecular subtype in Chinese people. Kaplan–Meier curves implicated that high SKA3 expression was related to a poor prognosis in female early breast cancer patients. Cox regression models showed that high SKA3 expression could be used as an independent risk factor for female early breast cancer. Four signaling pathways were enriched in the high SKA3 expression group, including mTORC1 signaling pathway, MYC targets v1, mitotic spindle, estrogen response early. Besides, the SKA3 expression level was associate with infiltrating levels of activated CD4 T cells and eosinophils in breast cancer. Conclusion High SKA3 expression correlates with poor prognosis and immune infiltrates in breast cancer. SKA3 may become a biomarker for the prognosis of breast cancer.

SKA3 targeted therapies in cancer precision surgery: bridging bench discoveries to clinical applications – review article

“…Brain metastases drastically decrease the 1-year survival rate to a mere 20% in BRCA patients, emphasizing the critical need for biomarkers predicting such metastases to guide timely interventions and avoid inappropriate surgical approaches 90 , 91 . The involvement of SKA3 in BRCA brain metastasis might intersect with the ER and PR status, as high SKA3 expression correlates with ER-negative and PR-negative statuses 32 , known risk factors for brain metastasis in BRCA patients 92 . This suggests a potential role of SKA3 in influencing ER and PR expression status, thereby contributing to the process of brain metastasis.…”

“…Zhong et al . 32 found mTORC1 signaling pathway, MYC targets v1, mitotic spindle, estrogen response early were enriched in the high SKA3 expression group through the Gene Set Enrichment Analysis and the expression level of SKA3 was associated with infiltrating levels of activated CD4+ T cells and eosinophils in BRCA. mTORC1 is a downstream molecule of the PI3K-AKT signaling pathway, which plays an important role in BRCA cell growth, proliferation, survival, and tumor resistance to endocrine therapies 41 – 43 .…”

“…In BRCA patients, many studies proved that SKA3 was overexpressed in BRCA tissues 32 – 35 and correlated with poor prognosis of BRCA patients, containing poor overall survival, relapse-free survival, postprogression survival, and distant metastasis-free survival 32 – 34 , 36 . In addition, the expression of SKA3 was also found to be associated with age, tumor classification, lymph node classification, tumor-node-metastasis stage, estrogen receptor (ER), progesterone receptor (PR), molecular subtype, and race 32 . Moreover, the rearrangements of SKA3 in BRCA were found to involve in potential mechanism on the growth and proliferation of BRCA cells 37 .…”

A comprehensive prognostic score for head and neck squamous cancer driver genes and phenotype traits

“…The high APMHO subgroup showed enrichment in several tumor-associated pathways including hypoxia, unfolded protein response, mTORC1 and Glycolysis signaling, while the KRAS signaling pathway was relatively downregulated in this subgroup. mTORC1 signaling pathway has emerged as a crucial player in the oncogenesis and development of HNSCC, and a mTORC1-related gene signature was documented as a novel prognostic factor for HNSCC [ 56 ], showing higher mTORC1 immunopositivity conferred worse outcomes in older and higher-risk cases [ 57 ]. However, the correlation of mTORC1 target pathways with tumor microenvironment and prognosis in HNSCC is unclear.…”

SKA1/2/3 is a biomarker of poor prognosis in human hepatocellular carcinoma

“…SKA3 is significantly particapted in the processes of chromosome cohesion maintenance and silencing of spindle checkpoint during mitosis ( 21 ). In the female patients with early breast cancer, the close association of the elevated SKA3 expression with a poor prognosis was observed ( 22 ). The inhibition of cell proliferation, induction of cell cycle arrest in the G1/S phase, as well as in vitro and in vivo tumorigenesis, were significantly connected to the downregulation of SKA3.…”