<p>Usefulness of Circulating Methylated p16 as a Noninvasive Molecular Biomarker for Hepatitis C-Related Hepatocellular Carcinoma with Normal Serum Alpha-Fetoprotein Levels</p>

Abstract

Background: Screening of hepatocellular carcinoma (HCC) is challenged especially in patients with normal alpha-fetoprotein (AFP) levels. Aberrant p16 methylation has been implicated in HCC. Objectives and Aims: This study aimed to assess serum methylated p16 (MP16) expression levels and to evaluate MP16 diagnostic performance in HCC detection among HCVinfected Egyptian patients with normal AFP levels. Methods: MP16 levels were quantified using real-time PCR in 230 serum samples (30 healthy controls, 95 with HCV-HCC, 40 with chronic hepatitis C "CHC" and 65 with HCV cirrhosis). Diagnostic performance of MP16 for diagnosis of HCC was done using receiver operator characteristic curve analysis. Results: Serum MP16 levels were significantly higher in HCC than CHC, cirrhosis, and healthy subjects and significantly higher in HCC with normal AFP levels than those with higher AFP. ROC curves revealed promising diagnostic performance for MP16 in discriminating HCC with normal AFP levels from non-HCC cases. This predictive ability improved by combining MP16 and AFP (AUC of 0.872 with 100% sensitivity, 76.5% specificity, 79.1% positive predictive value, 100% negative predictive value, and 87.5% accuracy). Conclusion: MP16 can be a potential noninvasive molecular biomarker for HCC detection in patients with hepatic mass(es) and normal AFP levels especially in those where liver biopsy and radiological imaging cannot be done.

Integrative bioinformatics and experimental analysis revealed TEAD as novel prognostic target for hepatocellular carcinoma and its roles in ferroptosis regulation

“…At present, we apply chemoradiotherapy and surgery to deal with the early stage of HCC in clinical and obviously improve the patients' condition [4]. However, the majority of patients are diagnosed in advanced stages [5]. In addition, the molecular pathogenesis of HCC varies on the basis of the different etiologies and genotoxic insults [6].…”