Document Type : Original Article
Authors
1
Department of Molecular Biology*,Genetic Engineering and Biotechnology Research Institute EL-Sadat University
2
Departments of Clinical Biochemistry National Liver Institute, Menoufia University
Abstract
Objective: to evaluate the miRNA -155 expression in patients with chronic HCV infection & correlate it with hepatitis C viral load and treatment response.
Background: MicroRNAs (miRNAs), are small, single-stranded, noncoding RNAs that consist of 20 to 25 base pair (bp).It is a class of small RNAs that regulate mRNA translation and function as oncogenes or tumor suppressor genes. In patients infected with HCV, miRNA-155 expression levels were markedly increased and promote hepatocyte proliferation and tumorigenesis by modulating Wnt signaling.
Subjects and Methods: This study was conducted on 20 HCC patients, 60chronic liver disease (CLD) patients due to HCV infection subdivided in to20 patients with HCVnaive treatment,20 patients responder treatment to interferon,20 patients non responder treatment to interferon patients and 20 healthy subjects matching age and gender. Serum AFP was measured for all participants. The relative expression of miRNA-155 was determined in whole blood samples using Real-time polymerase chain reaction.
Results: The results revealed over expression of miRNA-155 in each of HCC patient group, patients with HCVnaive treatment and patients non responder to interferon treatment. However, miRNA-155 showed down expression inpatients responder to interferon treatment.miRNA-155 expression was positively correlated with presence of cirrhosis, increased number of focal lesions, larger size of tumor, advanced tumor stage and presence of vascular invasion. From ROC curve analysis, the best cutoff of miRNA-155 chosen to differeniate HCC cases from non HCC subjects was 3.41RQs(Fold expression), and at this point the sensitivity, specificity, +ve predictive value (PPV), -ve predictive value (NPV) and Accuracy were 88.8%,91%, 92.4% ,89.5%,91.4% respectively. For AFP the best cutoff was 85.3ng/ml at this cutoff point the Sensitivity, Specificity , PPV, NPV, Accuracy were (76.2 % , 87.3 % ,, 90.2 % , 72.41 %, 81.0%). Furthermore, combined use of serum AFP and circulating miRNA-155for detection of HCC cases, had the advantage over the use of AFP alone as the sensitivity, specificity, PPV, NPP and overall accuracy were increased (89.32 %, 91.9 %, 93.5%, 90.71 % and 92 % respectively).
Conclusion: miRNA-155 expression might be correlated with hepatitis C viral load and treatment response. Also, miRNA-155could be a novel diagnostic and prognostic biomarker for detection of HCC in combination with AFP as well as it could serves as a potential therapeutic target for HCV and HCC infection
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