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

Background: Hepatocellular carcinoma (HCC) is reported as the sixth most common cancer worldwide and is the third most frequent cause of cancer-related deaths. MiRNAs are a set of small, single stranded, noncoding RNA molecules that negatively regulate gene expression at the posttranscriptional level. Several miRNAs were found to be frequently deregulated in HCC and some specific miRNAs were found to be associated with the clinicopathological features of HCC. Objectives: The aim of this study was to investigate whether the gene expression levels of miRNA-21 and miRNA-215 could differentiate HCC from chronic HCV infection in order to develop a non-invasive diagnostic tool for HCC. Subjects and Methods: The current study analysed the expression of mature miRNA-21 and miRNA-215 in serum by a singleplex TaqMan two step stem loop quantitative real-time reverse-transcription PCR (qRT-PCR) in 40 patients diagnosed with HCC, 40 chronic HCV without HCC and 40 apparently healthy subjects as a control group using cel mir-39 as a normalization control. Results: Expression of miR-21 was significantly downregulated in HCC patients than in the HCV non cirrhosis patients (P= 0.007). ROC analysis for expression of miR-21 for discriminating HCC patients from HCV non cirrhosis patients showed that at the cut-off value of {u2264}1.4468, the sensitivity and specificity for this marker were 70% and 68.2%, respectively with AUC was 0.712. Expression level of miRNA 21 was showed to be significant in predicting HCC diagnosis from HCV non cirrhosis (OR=5; 95% CI=1.6-15.4; p=0.004). There was significant positive correlation between expression of miR-21 and miR-215 (r=0.783& p<0.001). There was no association between expression of miR-215 and HCC nor chronic HCV (p=0.474). Conclusions: MiR-21 may play an important role in pathogenesis of HCC. It could be used as a diagnostic tool for HCC & carry 5 times risk of HCC susceptibility among HCV non cirrhotic patients

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