Department of Infectious Disease, The Eighth Affiliated Hospital of Sun Yat-sen University, Shenzhen City, China.
Medicine (Baltimore). 2023 Sep 22;102(38):e34826. doi: 10.1097/MD.0000000000034826.
Hepatocellular carcinoma (HCC) poses a global health challenge. Effective biomarkers are required for early diagnosis to improve survival rates of patients with HCC. Spindle and kinetochore-associated complex subunits 1 (SKA1) is essential for proper chromosome segregation in the mitotic cell cycle. Previous studies have shown that overexpression of SKA1 is associated with a poor prognosis in various cancers. The expression, prognostic value, and clinical functions of SKA1 in HCC were evaluated with several bioinformatics web portals. Additionally, we identified target long non-coding RNAs (lncRNAs) and microRNAs by analyzing messenger RNA (mRNA)-miRNA and miRNA-lncRNA interaction data and elucidated the potential competing endogenous RNA (ceRNA) mechanism associated with SKA1. High SKA1 expression was associated with poor prognosis in patients with HCC. Furthermore, multivariate Cox regression analysis revealed that SKA1 expression was an independent prognostic factor for HCC. GO and KEGG analyses showed that SKA1 is related to the cell cycle checkpoints, DNA replication and repair, Rho GTPases signaling, mitotic prometaphase, and kinesins. Gene set enrichment analysis revealed that high levels of SKA1 are associated with cancer-promoting pathways. DNA methylation of SKA1 in HCC tissues was lower than that in normal tissues. Ultimately, the following 9 potential ceRNA-based pathways targeting SKA1 were identified: lncRNA: AC026401.3, Small Nucleolar RNA Host Gene 3 (SNHG3), and AC124798.1-miR-139-5p-SKA1; lncRNA: AC26356.1, Small Nucleolar RNA Host Gene 16 (SNHG16), and FGD5 Antisense RNA 1-miR-22-3p-SKA1; lncRNA: Cytoskeleton Regulator RNA (CYTOR), MIR4435-2 Host Gene, and differentiation antagonizing non-protein coding RNA-miR-125b-5p-SKA1. SKA1 expression levels significantly correlated with immune cell infiltration and immune checkpoint genes in the HCC tissues. SKA1 is a potential prognostic biomarker for HCC. This study provides a meaningful direction for research on SKA1-related mechanisms, which will be beneficial for future research on HCC-related molecular biological therapies and targeted immunotherapy.
肝细胞癌 (HCC) 是全球健康面临的挑战。需要有效的生物标志物进行早期诊断，以提高 HCC 患者的生存率。纺锤体和着丝粒相关复合物亚基 1 (SKA1) 对于有丝分裂细胞周期中染色体的正确分离至关重要。先前的研究表明，SKA1 的过表达与各种癌症的不良预后相关。通过分析信使 RNA (mRNA)-miRNA 和 miRNA-lncRNA 相互作用数据，使用几个生物信息学网络门户评估了 SKA1 在 HCC 中的表达、预后价值和临床功能。此外，我们通过分析信使 RNA (mRNA)-miRNA 和 miRNA-lncRNA 相互作用数据，鉴定了 SKA1 的靶长链非编码 RNA (lncRNA) 和 microRNA，并阐明了与 SKA1 相关的潜在竞争性内源 RNA (ceRNA) 机制。高 SKA1 表达与 HCC 患者的预后不良相关。此外，多变量 Cox 回归分析显示，SKA1 表达是 HCC 的独立预后因素。GO 和 KEGG 分析表明，SKA1 与细胞周期检查点、DNA 复制和修复、Rho GTPases 信号、有丝分裂前中期和驱动蛋白有关。基因集富集分析表明，高水平的 SKA1 与促进癌症的途径有关。HCC 组织中 SKA1 的 DNA 甲基化水平低于正常组织。最终，确定了以下 9 个针对 SKA1 的潜在基于 ceRNA 的途径：lncRNA：AC026401.3、Small Nucleolar RNA Host Gene 3 (SNHG3) 和 AC124798.1-miR-139-5p-SKA1；lncRNA：AC26356.1、Small Nucleolar RNA Host Gene 16 (SNHG16) 和 FGD5 Antisense RNA 1-miR-22-3p-SKA1；lncRNA：Cytoskeleton Regulator RNA (CYTOR)、MIR4435-2 Host Gene 和 differentiation antagonizing non-protein coding RNA-miR-125b-5p-SKA1。SKA1 表达水平与 HCC 组织中的免疫细胞浸润和免疫检查点基因显著相关。SKA1 是 HCC 的潜在预后生物标志物。这项研究为 SKA1 相关机制的研究提供了有意义的方向，这将有助于未来 HCC 相关分子生物学治疗和靶向免疫治疗的研究。
