Enolase-1 serves as a biomarker of diagnosis and prognosis in hepatocellular carcinoma patients

Abstract

Weiwei Zhu,1,2,* Hongqiang Li,1,2,* Yan Yu,1,2 Jianan Chen,1,2 Xiaolong Chen,1,2 Fang Ren,2 Zhigang Ren,1,2 Guangying Cui1,2 1Precision Medicine Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China; 2Key Laboratory of Clinical Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China *These authors contributed equally to this work Background: Hepatocellular carcinoma (HCC) is an aggressive malignancy with high incidence rate and poor prognosis. Enolase-1 (ENO1), a key glycolytic enzyme, has been implicated in the tumorigenesis of various cancers. However, its diagnostic value and clinical significance in HCC are unclear.Methods: Data of 374 HCC tissues and 50 nontumor tissues were retrieved from The Cancer Genome Atlas database, and the expression level of ENO1 mRNA in HCC was evaluated. In addition, a meta-analysis of 12 HCC cohorts deposited in the Gene Expression Omnibus database was conducted to determine ENO1 expression levels. The diagnostic power of ENO1 in distinguishing HCC tissues from non-HCC tissues was confirmed by receiver operating characteristic (ROC) curve analysis. A tissue microarray comprising 93 HCC specimens and 87 adjacent normal specimens was used to validate ENO1 expression, and its prognostic value in HCC was ascertained by Kaplan–Meier analysis and Cox regression models. In addition, the gene set enrichment analysis was performed to predict the molecular mechanism of ENO1 action in HCC.Results: ENO1 was overexpressed in HCC tissues and associated with worse outcomes in terms of overall survival (OS) (P<0.01) and disease-free survival (P<0.01). ENO1 expression (P<0.01) was an independent prognostic variable for the OS of HCC patients. Moreover, as per the ROC curve analysis, it had good diagnostic power as well. In addition, elevated expression of ENO1 was significantly correlated with the cell cycle and DNA replication pathway, consistent with its association with pro-proliferative genes such as MKI67, PCNA, CDK4, CDK2, and MELK.Conclusion: ENO1 was markedly upregulated and was an oncogene-associated protein in HCC. It is a promising prognostic and diagnostic biomarker for HCC. Keywords: ENO1, hepatocellular carcinoma, diagnosis, proliferation, cell cycle

Keywords

• ENO1
• hepatocellular carcinoma
• diagnosis
• proliferation
• cell cycle