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

Wael Abd Elgwad Elsewify; Elham Ahmed Hassan; Mohamed A Mekky; Abeer Sharaf El-Din Abd El-Rehim; Zain El-Abdeen Ahmed Sayed; Mohamed Omar Abdel Malek; Tarek T H ElMelegy; Abeer Sabry

doi:10.2147/IJGM.S249272

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

Int J Gen Med. 2020 Apr 30:13:147-155. doi: 10.2147/IJGM.S249272. eCollection 2020.

Authors

Wael Abd Elgwad Elsewify¹, Elham Ahmed Hassan², Mohamed A Mekky², Abeer Sharaf El-Din Abd El-Rehim², Zain El-Abdeen Ahmed Sayed³, Mohamed Omar Abdel Malek², Tarek T H ElMelegy⁴, Abeer Sabry⁵

Affiliations

¹ Department of Internal Medicine, Faculty of Medicine, Aswan University, Aswan, Egypt.
² Department of Gastroenterology and Tropical Medicine, Faculty of Medicine, Assiut University, Assiut, Egypt.
³ Department of Internal Medicine, Faculty of Medicine, Assiut University, Assiut, Egypt.
⁴ Department of Clinical Pathology, Faculty of Medicine, Assiut University, Assiut, Egypt.
⁵ Department of Internal Medicine, Faculty of Medicine, Helwan University, Cairo, Egypt.

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 HCV-infected 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.

Keywords: alpha-fetoprotein; hepatitis C virus; hepatocellular carcinoma; methylated p16; quantitative real-time PCR.