Elsewify Wael Abd Elgwad, Hassan Elham Ahmed, Mekky Mohamed A, Abd El-Rehim Abeer Sharaf El-Din, Sayed Zain El-Abdeen Ahmed, Abdel Malek Mohamed Omar, ElMelegy Tarek T H, Sabry Abeer
Department of Internal Medicine, Faculty of Medicine, Aswan University, Aswan, Egypt.
Department of Gastroenterology and Tropical Medicine, Faculty of Medicine, Assiut University, Assiut, Egypt.
Int J Gen Med. 2020 Apr 30;13:147-155. doi: 10.2147/IJGM.S249272. eCollection 2020.
Screening of hepatocellular carcinoma (HCC) is challenged especially in patients with normal alpha-fetoprotein (AFP) levels. Aberrant p16 methylation has been implicated in HCC.
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.
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.
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).
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.
肝细胞癌（HCC）的筛查面临挑战，尤其是在甲胎蛋白（AFP）水平正常的患者中。p16异常甲基化与HCC有关。
本研究旨在评估血清甲基化p16（MP16）的表达水平，并评估MP16在检测AFP水平正常的埃及HCV感染患者HCC中的诊断性能。
使用实时PCR对230份血清样本（30名健康对照、95名HCV-HCC患者、40名慢性丙型肝炎“CHC”患者和65名HCV肝硬化患者）中的MP16水平进行定量。使用受试者操作特征曲线分析评估MP16对HCC的诊断性能。
HCC患者的血清MP16水平显著高于CHC、肝硬化患者和健康受试者，AFP水平正常的HCC患者的血清MP16水平显著高于AFP水平较高的患者。ROC曲线显示MP16在区分AFP水平正常的HCC与非HCC病例方面具有良好的诊断性能。通过将MP16和AFP联合使用，这种预测能力得到了提高（曲线下面积为0.872，灵敏度为100%，特异性为76.5%，阳性预测值为79.1%，阴性预测值为100%，准确率为87.5%）。
MP16可能是检测肝脏有肿块且AFP水平正常患者HCC的潜在非侵入性分子生物标志物，尤其是在无法进行肝活检和放射影像学检查的患者中。
