ESPL1 is Elevated in Hepatocellular Carcinoma and Predicts Prognosis

Abstract

Rui Song,1,2,* Juntao Huang,1,2,* Chenglei Yang,1,2 Yuankuan Li,1,2 Guohua Zhan,1,2 Bangde Xiang1– 3,* 1Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning, People’s Republic of China; 2Key Laboratory of Early Prevention and Treatment for Regional High-Frequency Tumors, Ministry of Education, Nanning, People’s Republic of China; 3Guangxi Liver Cancer Diagnosis and Treatment Engineering and Technology Research Center, Nanning, People’s Republic of China*These authors contributed equally to this workCorrespondence: Bangde Xiang, Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, 71 Hedi Road, Qingxiu District, Nanning, Guangxi, 530021, People’s Republic of China, Tel [phone], Email [email protected]: The extra spindle pole bodies-like 1 (ESPL1) gene is associated with malignant biological behaviors in several tumors. Nevertheless, the correlation between hepatocellular carcinoma (HCC) and ESPL1 has not been determined. The present study analyzed the molecular function and prognostic value of ESPL1 in HCC.Patients and Methods: Samples from 121 HCCs and 119 adjacent normal tissue specimens were subjected to next-generation sequencing. Clinicopathological and genetic data of HCC patients in The Cancer Genome Atlas (TCGA) were also collected. ESPL1 expression was assessed in 20 pairs of HCC and normal liver specimens by qRT-PCR and immunohistochemistry (IHC). The prognostic value of ESPL1 expression was determined by Cox univariate and multivariate regression analyses. ESPL1-related co-expressed genes were evaluated by weighted gene co-expression network analysis (WGCNA). Processes and pathways involving ESPL1 in HCC were determined by Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. The prognostic values of hub genes were determined by joint effect survival analysis.Results: RNA-Seq, RT-qPCR and IHC showed that ESPL1 expression was significantly higher in HCC than in normal liver tissues. Increased ESPL1 expression, greater tumor size and advanced BCLC stage were independently prognostic of poorer overall survival; and increased ESPL1 and advanced BCLC stage were independently prognostic of poorer recurrence-free survival. WGCNA showed that 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-expressed genes might be involved in the cell cycle and cell division of HCC. Joint effect survival analysis showed that the mortality rate was approximately 3.37 times higher in HCC patients with high than low expression of ESPL1, GTSE1, BUB1B, PRC1, KIF23, and TOP2A.Conclusion: ESPL1 might be associated with cell cycle and might be an effective prognostic indicator in patients with HCC.Keywords: hepatocellular carcinoma, extra spindle pole bodies-like 1, prognosis

Keywords

• hepatocellular carcinoma
• extra spindle pole bodies-like 1
• prognosis