Screening for Lipid-Metabolism-Related Genes and Identifying the Diagnostic Potential of ANGPTL6 for HBV-Related Early-Stage Hepatocellular Carcinoma

Lipid metabolic reprogramming is one of the hallmarks of hepatocarcinogenesis and development. Therefore, lipid-metabolism-related genes may be used as potential biomarkers for hepatocellular carcinoma (HCC). This study aimed to screen for genes with dysregulated expression related to lipid metabolism in HCC and explored the clinical value of these genes. We screened differentially expressed proteins between tumorous and adjacent nontumorous tissues of hepatitis B virus (HBV)-related HCC patients using a Nanoscale Liquid Chromatography–Tandem Mass Spectrometry platform and combined it with transcriptomic data of lipid-metabolism-related genes from the GEO and HPA databases to identify dysregulated genes that may be involved in lipid metabolic processes. The potential clinical values of these genes were explored by bioinformatics online analysis tools (GEPIA, cBioPortal, SurvivalMeth, and TIMER). The expression levels of the secreted protein (angiopoietin-like protein 6, ANGPTL6) in serum were analyzed by ELISA. The ability of serum ANGPTL6 to diagnose early HCC was assessed by ROC curves. The results showed that serum ANGPTL6 could effectively differentiate between HBV-related early HCC patients with normal serum alpha-fetoprotein (AFP) levels and the noncancer group (healthy participants and chronic hepatitis B patients) (AUC = 0.717, 95% CI: from 0.614 to 0.805). Serum ANGPTL6 can be used as a potential second-line biomarker to supplement serum AFP in the early diagnosis of HBV-related HCC.