ESPL is elevated in Hepatocellular Carcinoma and Predicts Prognosis

Abstract Background: Extra spindle pole bodies-like 1 (ESPL1) are associated with malignant biological behaviors in several tumors. Nevertheless, the correlation between hepatocellular carcinoma (HCC) and ESPL1 has not yet been confirmed. The objective of this paper is to analyze the molecular function together with the prognosis value of ESPL1 in HCC.Methods: Firstly, we conducted next-generation sequencing on 121 HCC tissues and 119 normal adjacent normal tissues and collected clinicopathological and genetic data of HCC patients in The Cancer Genome Atlas (TCGA). Secondly, we verified the ESPL1 expression in another twenty pairs of HCC specimens by qRT-PCR. Subsequently, the prognostic value of ESPL1 was investigated through Cox univariate and multivariate regression analysis. Finally, weighted gene co-expression network analysis (WGCNA) was performed to define ESPL1-related co-expressed genes. Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were used to analyze the process and pathway of ESPL1 in HCC. The prognostic value for the hub genes was explored through joint effect survival analysis.Results: RNA-Seq and RT-qPCR data showed that raised ESPL1 in HCC tissues relative to normal tissues (P<0.001). Clinically, ESPL1 (HR=2.004, 95%CI=1.072-3.743, P=0.032), tumor size (HR=2.468, 95%CI=1.137-5.354, P=0.021) and advanced BCLC stage (HR=1.956, 95%CI=1.037-3.692, P=0.038) were independent prognostic factors for poor OS; ESPL1 ((HR=1.653, 95%CI=1.032-2.645, P=0.036) and advanced BCLC stage (HR=2.217, 95%CI=1.348-3.646, P=0.002) were independent prognostic factors for poor RFS. WGCNA showed the top 10 co-expressed genes associated with ESPL1 were GTSE1, KIF18B, BUB1B, GINS1, PRC1, KIF23, KIF18A, TOP2A, NEK2 and FANCD2. Enrichment analysis indicated that ESPL1 and its co-expression genes might be involved in the cell cycle and cell division of HCC. The joint effect survival analysis suggested that the mortality rate of HCC patients with all high expression of ESPL1, GTSE1, BUB1B, PRC1, KIF23, and TOP2A was approximately 3.37 times higher than that of patients with all low expression. Immune infiltration analysis demonstrated that infiltration by B cells, dendritic cells, and Treg cells were positively associated with ESPL1.Conclusion: Our outcomes exhibit that ESPL1 might be associated with immunosuppression and probably is an effective prognostic indicator in HCC patients.