High Squalene Epoxidase in Tumors Predicts Worse Survival in Patients With Hepatocellular Carcinoma: Integrated Bioinformatic Analysis on NAFLD and HCC

摘要

This study aimed to identify candidate biomarkers for predicting outcomes in nonalcoholic fatty liver disease (NAFLD) and hepatocellular carcinoma (HCC). Using Gene Expression Omnibus and The Cancer Genome Atlas (TCGA) databases, we identified common upregulated differential expressed genes (DEGs) in patients with NAFLD/nonalcoholic steatohepatitis (NASH) and HCC and conducted survival analysis of these upregulated DEGs with HCC outcomes. Two common upregulated DEGs including squalene epoxidase (SQLE) and EPPK1 messenger RNA (mRNA) were significantly upregulated in NAFLD, NASH, and HCC tissues, both in GSE45436 ( P < .001) and TCGA profile ( P .05). For validation, SQLE upregulation contributed to significantly worse OS in patients wih HCC using Kaplan-Meier plotter analysis (hazard ratio = 1.43, 95% confidence interval: 1.01-2.02, log-rank P = .043). In addition, high level of SQLE significantly associated with advanced neoplasm histologic grade, advanced AJCC stage, and α-fetoprotein elevation ( P = .036, .045, and .029, respectively). Squalene epoxidase is associated with OS and DFS and serves as a novel prognostic biomarker for patients with HCC.