Preliminary investigation of nicotinamide N-methyltransferase as an HBV-specific biomarker for hepatocellular carcinoma diagnosis.

Abstract

BackgroundNicotinamide N-methyltransferase (NNMT), a metabolic enzyme in the liver, has been implicated in various biological processes, and its high expression in hepatocellular carcinoma has been linked to tumor metastasis and poor prognosis. However, its potential as a serum biomarker for hepatocellular carcinoma diagnosis remains unexplored.MethodsA total of 172 subjects were included in this study, consisting of 71 hepatocellular carcinoma patients (64 with hepatitis B virus (HBV)-associated hepatocellular carcinoma and 7 with non-HBV-associated hepatocellular carcinoma), as well as 70 healthy controls and 31 HBV-infected individuals. Serum NNMT levels were measured, and clinical-pathological correlations were analyzed. The diagnostic efficacy of serum NNMT for HBV-related hepatocellular carcinoma was evaluated using receiver operating characteristic (ROC) curve analysis.ResultsSerum NNMT levels were significantly elevated in HBV-infected individuals and correlated with poorer prognosis, including reduced overall survival and shorter disease-free survival. Kaplan-Meier analysis revealed that low NNMT expression was associated with longer overall survival (75 vs. 12 months, P < 0.0001) and disease-free survival (21.5 vs. 5 months, P < 0.01). In HBV-related hepatocellular carcinoma patients, NNMT levels correlated with biochemical markers including alfa-fetoprotein, aspartate transaminase, triglycerides, total cholesterol, low-density lipoprotein, apolipoprotein B, TB, and albumin, with decreased albumin, and high-density lipoprotein levels promoting NNMT expression. ROC analysis showed that NNMT outperformed alfa-fetoprotein (area under the curve (AUC) 0.869 vs. 0.775), with a sensitivity of 95.2%, specificity of 87.9%, and a combined AUC of 0.947, demonstrating its superior diagnostic value for HBV-related hepatocellular carcinoma.ConclusionsSerum NNMT is a promising biomarker for predicting the risk of hepatocellular carcinoma in HBV-infected individuals and may serve as an indicator for the prognosis of hepatocellular carcinoma patients.