HCC-miR: A Simple, Noninvasive, and Sensitive Model for Early Diagnosis of HCV-Associated Hepatocellular Carcinoma

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BACKGROUND: Hepatocellular carcinoma (HCC) is the most common primary liver malignancy and a major cause of cancer-related mortality worldwide. Chronic hepatitis C virus (HCV) infection remains the predominant etiological factor in Egypt. The limited sensitivity and specificity of alpha-fetoprotein (AFP) continue to hinder early HCC detection. This study aimed to assess the diagnostic significance of circulating microRNA-155 (miRNA-155) expression in HCV-related HCC and to develop a novel, noninvasive diagnostic model combining miRNA-155 with routine biomarkers. Methods: A total of 42 HCV-positive HCC patients, 83 patients with liver cirrhosis (LC), and 20 healthy controls were enrolled. Clinical, hematologic, and biochemical parameters were analyzed. Circulating miRNA-155 levels were quantified by quantitative real-time PCR and normalized to U6 RNA. Receiver operating characteristic (ROC) curve analysis and multivariate discriminant analyses were used to develop a composite diagnostic model integrating AFP, albumin, platelet count, INR, AST/ALT ratio, and miRNA-155, designated the HCC-miR Score. RESULTS: Liver function tests and hematologic indices showed progressive deterioration from controls to LC and HCC groups. miRNA-155 expression was significantly elevated in HCC (6.71 ° 3.38) compared with LC (5.44 ° 2.31) and controls (1.27 ° 0.68) (p < 0.0001). The HCC-miR Score demonstrated superior diagnostic accuracy (AUC = 0.753) to AFP alone (AUC = 0.713), achieving 100% sensitivity and 68% specificity at a cutoff value of 0.32. The model effectively discriminated early-stage, small-sized, and well-differentiated tumors from cirrhotic cases, outperforming AFP across all subgroups. CONCLUSION: Circulating miRNA-155 is markedly upregulated in HCV-related HCC and correlates strongly with disease progression. The novel HCC-miR Score represents a simple, sensitive, and noninvasive model for the early diagnosis of HCC in high-risk HCV patients.

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