Diagnostic Utility of FAR1 Methylation Levels in Hepatocellular Carcinoma Patients Undergoing Liver Transplantation

BACKGROUND Recent research has highlighted DNA methylation as a promising diagnostic biomarker for hepatocellular carcinoma (HCC). Fatty Acyl-CoA Reductase 1 (FAR1) exhibits a high propensity for methylation in HCC. This study aimed to evaluate diagnostic and prognostic potential of FAR1 methylation in liver transplantation (LT) recipients with HCC. MATERIAL AND METHODS This analysis used droplet digital polymerase chain reaction to quantify FAR1 methylation levels in stored pretransplant blood samples. The study cohort (n=48) comprised 25 liver cirrhosis patients with HCC, 13 with cirrhosis but no HCC, and 10 healthy donors. RESULTS Median and mean methylation levels of FAR1 in these groups were 4 copies, zero copies, and zero copies, and 31.6±74.5, 1.5±3.5, and 0.1±0.4 copies, respectively (p<0.001). Receiver operating characteristic curve analysis revealed area under the curve of 0.832 for FAR1, outperforming a-fetoprotein (AFP; 0.737) and protein induced by vitamin K absence or antagonist-II (PIVKA-II; 0.732). A cut-off value of 1 copy for FAR1, defined by Youden's Index (J=0.599), yielded sensitivity of 82.6% and specificity of 77.3%, surpassing diagnostic capacities of AFP and PIVKA-II. Combining FAR1 >1 copy with AFP >7.5 ng/mL or PIVKA-II >40 mAU/mL increased the sensitivity to 91.3%, with specificity of 72.7% and overall accuracy of 82.2%. There was no significant correlation between FAR1 methylation levels and tumor recurrence or overall survival when using a cut-off of 1 copy. CONCLUSIONS These findings suggest that FAR1 methylation is a valuable biomarker for diagnosing HCC in patients with advanced liver disease awaiting transplantation. Further large-scale investigations are necessary to validate clinical efficacy.