Integrated analysis of SKA1-related ceRNA network and SKA1 immunoassays in HCC: A study based on bioinformatic

Abstract

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.