The necessity for early detection and hence improving the outcome of treatment of hepatocellular carcinoma (HCC) is critical especially in Hepatitis C virus (HCV)-Genotype 4 induced cases. In our current work, we examined the miRNA-152 and DNMT-1 expression in chronic liver disease (CLD) due to HCV genotype 4 infection with/without cirrhosis and HCC patients as an attempt to evaluate the potential benefits of these new circulating, noninvasive, prognostic, epigenetic markers for liver cirrhosis and carcinogenesis of Egyptian patients. Eighty subjects were included in this study, divided into two groups; group I (40 patients) were classified into subgroup Ia (CLD without cirrhosis, n = 18) and subgroup Ib (CLD with cirrhosis, n = 22), group II (CLD patients with HCC, n = 20), and control (Healthy volunteer, n = 20). The expression of miRNA-152 and DNMT-1 genes were analyzed using Real-Time PCR. MiRNA-152 showed a persistent and significant downregulation in all diseased groups, which was in consistence with the progression of the disease toward the HCC stage. DNMT-1 showed upregulation in all diseased groups when compared to control and subgroup Ia. The miRNA-152 was shown to correlate inversely with DNMT-1 in subgroup Ia, Ib and group II (r = −0.557, p < 0.01), (r = −0.850, p < 0.001) and (r = −0.544, p < 0.02) respectively. In addition, miRNA-152 and DNMT-1 showed a diagnostic ability to discriminate between cases of cirrhosis and HCC against CLD without cirrhosis (p < 0.01), while DNMT-1 did not, except between HCC and cirrhotic cases. Furthermore, both genes can be considered as predictor and prognostic parameters for cirrhosis (OR = 1.041, p = 0.043) and (OR = 1.039, p = 0.04) respectively, while miRNA-152 alone is proved as a prognostic marker for HCC (OR = 1.003, p = 0.044). Finally, the persistent reverse correlation between miRNA-152 with DNMT-1 prompts their use as noninvasive prognostic biomarkers for HCV induced liver cirrhosis and HCC in HCV Genotype 4 patients.

早期发现并因此改善肝细胞癌 (HCC) 治疗结果的必要性至关重要，尤其是在丙型肝炎病毒 (HCV)-基因型 4 诱导的病例中。在我们目前的工作中，我们检查了 miRNA-152 和 DNMT-1 在慢性肝病 (CLD) 中的表达，这是由于 HCV 基因型 4 感染伴/不伴肝硬化和 HCC 患者，试图评估这些新的循环非侵入性的潜在益处，埃及患者肝硬化和癌变的预后、表观遗传标志物。本研究共纳入八十名受试者，分为两组；I 组（40 名患者）分为 Ia 亚组（无肝硬化的 CLD，n  = 18）和 Ib 亚组（有肝硬化的 CLD，n  = 22），II 组（有 HCC 的 CLD 患者，n = 20）和对照（健康志愿者，n  = 20）。使用实时 PCR 分析 miRNA-152 和 DNMT-1 基因的表达。miRNA-152 在所有患病组中均表现出持续显着的下调，这与疾病向 HCC 阶段的进展相一致。与对照组和亚组 Ia 相比，DNMT-1 在所有患病组中均显示上调。在 Ia、Ib 和 II 组 ( r  = -0.557, p  < 0.01), ( r  = -0.850, p  < 0.001) 和 ( r  = -0.544, p < 0.02) 分别。此外，miRNA-152 和 DNMT-1 显示出区分肝硬化和 HCC 病例与无肝硬化 CLD 的诊断能力（p  < 0.01），而 DNMT-1 则没有，除了 HCC 和肝硬化病例。此外，这两个基因都可以被认为是肝硬化的预测因子和预后参数（OR = 1.041，p  = 0.043）和（OR = 1.039，p  = 0.04），而单独的 miRNA-152 被证明是 HCC 的预后标志物（OR = 1.003，p  = 0.044）。最后，miRNA-152 与 DNMT-1 之间的持续反向相关性促使它们在 HCV 基因型 4 患者中用作 HCV 诱导的肝硬化和 HCC 的无创预后生物标志物。