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High spindle and kinetochore-associated complex subunit-3 expression predicts poor prognosis and correlates with adverse immune infiltration in hepatocellular carcinoma.


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

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Publications

High spindle and kinetochore-associated complex subunit-3 expression predicts poor prognosis and correlates with adverse immune infiltration in hepatocellular carcinoma.

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]

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