Thesis (Ph.D.) - Cairo University - Faculty of Medicine - Department of Clinical and Chemical Pathology

Background: Hepatocellular carcinoma (HCC) is the commonest primary tumor of the liver. MicroRNAs (miRNAs) can generate different functions for regulating RNA protein levels and balancing abnormalities. Single nucleotide polymorphisms (SNPs) in miRNAs were reported to increase patient susceptibility to cancer development and affect prognosis and survival. Objective: To evaluate MiRNA 196a2 (rs11614913) C>T and MiRNA 499 (rs3746444) A>G as potential biomarkers for HCV-related HCC development in Egyptian patients. Subjects and methods: A case-control study included 75 HCV-related HCC patients, 75 cirrhotic patients on top of HCV infection and 75 healthy controls. Genotyping of the candidate SNPs was performed by Real Time PCR. Liver and kidney function tests, hepatitis B and C markers and AFP were performed. Results: There was a significant difference in miRNA 499 (rs3746444) genotypes frequency between the three studied groups (p=0.009) and the combined microRNA 499 (AA+AG) genotypes were significantly higher in HCC cases than in cirrhosis and normal control groups (p=0.005). The frequency of the G allele was significantly lower in HCC cases than other groups (p=0.024) and significantly lower in HCC cases than normal control group (p=0.006) and [OR (95%CI) = 0.501 (0.304-0.825)]. Median AST, ALT, ALP, total bilirubin and direct bilirubin levels were found to be significantly lower in patients with GG genotype than those with (AA+AG) genotypes with (p = 0.002, 0.036, 0.006, 0.021 and 0.01) respectively. For miRNA 196a2 (rs11614913) C>T polymorphisms, no significant association was found with the risk for HCC development

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