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ABSTRACT: Background
Spindle and kinetochore-associated complex subunit 3 (SKA3) is a malignancy-associated gene that plays a critical role in the regulation of chromosome separation and cell division. However, the molecular mechanism through which SKA3 regulates tumor cell proliferation in hepatocellular carcinoma (HCC) has not been fully elucidated.Aim
To investigate the molecular mechanisms underlying the role of SKA3 in HCC.Methods
SKA3 expression, clinicopathological, and survival analyses were performed using multiple public database platforms, and the results were verified by Western blot and immunohistochemistry staining using collected clinical samples. Functional enrichment analyses were performed to evaluate the biological functions and molecular mechanisms of SKA3 in HCC. Furthermore, the Tumor Immune Estimation Resource and single-sample Gene Set Enrichment Analysis (ssGSEA) algorithms were utilized to investigate the abundance of tumor-infiltrating immune cells in HCC. The response to chemotherapeutic drugs was evaluated by the R package "pRRophetic".Results
We found that upregulated SKA3 expression was significantly correlated with poor prognosis in patients with HCC. Multivariable Cox regression analysis indicated that SKA3 was an independent risk factor for survival. GSEA revealed that SKA3 expression may facilitate proliferation and migratory processes by regulating the cell cycle and DNA repair. Moreover, patients with high SKA3 expression had significantly decreased ratios of CD8+ T cells, natural killer cells, and dendritic cells. Drug sensitivity analysis showed that the high SKA3 group was more sensitive to sorafenib, sunitinib, paclitaxel, doxorubicin, gemcitabine, and vx-680.Conclusion
High SKA3 expression led to poor prognosis in patients with HCC by enhancing HCC proliferation and repressing immune cell infiltration surrounding HCC. SKA3 may be used as a biomarker for poor prognosis and as a therapeutic target in HCC.
SUBMITTER: Zheng LL
PROVIDER: S-EPMC10494596 | biostudies-literature | 2023 Aug
REPOSITORIES: biostudies-literature
Zheng Lin-Lin LL Wang Ya-Ru YR Liu Zhen-Rong ZR Wang Zhi-Hao ZH Tao Chang-Cheng CC Xiao Yong-Gang YG Zhang Kai K Wu An-Ke AK Li Hai-Yang HY Wu Jian-Xiong JX Xiao Ting T Rong Wei-Qi WQ
World journal of gastrointestinal surgery 20230801 8
<h4>Background</h4>Spindle and kinetochore-associated complex subunit 3 (SKA3) is a malignancy-associated gene that plays a critical role in the regulation of chromosome separation and cell division. However, the molecular mechanism through which SKA3 regulates tumor cell proliferation in hepatocellular carcinoma (HCC) has not been fully elucidated.<h4>Aim</h4>To investigate the molecular mechanisms underlying the role of SKA3 in HCC.<h4>Methods</h4>SKA3 expression, clinicopathological, and surv ...[more]