Egypt is one of the highest prevalence rates of hepatitis C virus (HCV) infection worldwide. HCV is among major reasons for chronic liver diseases. MicroRNA (miRNAs), small noncoding regulatory molecules play a key role in the pathogenesis of liver. Circulating miRNAs represent potential noninvasive biomarkers for diagnosis and monitoring patients with liver diseases progression. To investigate the potential role of circulating miRNAs for surveillance of liver disease progression, we assessed the expression of 20 liver-related miRNAs in sera of 47 chronic hepatitis C Egyptian patients compared with 25 controls using quantitative reverse-transcription polymerase chain reaction assay. The sensitivity and specificity were evaluated using receiver operating characteristic (ROC) curve. The correlations between their levels and the clinicopathological features were assessed. Fourteen miRNAs showed upregulation and six miRNAs showed downregulation. ROC curve analyses revealed that the explored miRNAs could serve as valuable biomarkers for chronic hepatitis with an area under the curve ranged from 0.708 (95% confidence interval [95% CI], 0.587 to 0.829; P = 0.004) for miR-199 up to 0.974 (95% CI, 0.943 to 1.00; P < 0.001) for miR-23b. The expression level of miR-21 demonstrated significant correlation with age, liver enzymes, ALT/AST, and α-fetoprotein level. AST level was directly correlated with miR-122, while an inversely correlated with miR-23b. Fibrosis and steatosis stages possessed positive correlation with miR-199 expression and negative correlation with miR-27a and miR-93. In conclusion, miR-23b and miR-106 might be a useful biomarker for chronic hepatitis C (CHC). MiR-27a, miR-93, and miR-199 might have a potential role in the progression of liver diseases. Unravel the role of these miRNAs in CHC patients might lead to precise prognosis and management.
Summary
Background
To date few reports have pointed out the role of circulating miRNAs in discriminating metastatic liver tumors from primary hepatocellular (HCC) tumors. Such discrimination will have significant therapeutic and prognostic implications. The purpose of this study was to evaluate the potential value of a panel of HCC-related circulating miRNAs (miR-142, miR-182, miR-200a, mir-210, miR-211, miR-302b, miR-324, miR-338, miR-340 and miR-1246) as noninvasive biomarkers for discriminating primary HCC from metastatic tumors in the liver.
Methods
The expression level of the selected miRNAs was quantified by quantitative real time PCR in 33 patients with HCC, 22 patients with metastatic tumors in the liver, and 30 healthy volunteers as control. Mann-Whitney U test was used to evaluate the difference in miRNAs expression between primary and metastatic liver tumors and to study the associations between their relative expression levels and the clinicopathological factors. Receiver operating characteristic curve was used to evaluate the diagnostic value of the individual miRNAs.
Results
Statistical analyses revealed a differential expression in the level of serum miR-210 and miR-1246 between the two groups of patients. The sensitivity and specificity of miR-210, for differentiating HCC from metastatic malignancies in the liver were found to be 73.7% and 64.28%, respectively. Whilst, of miR-1246 were 72.2% and 67.8%, respectively. In addition, the differential expression of the two miRNAs was also found to be associated with clinicopathological parameters in the two studied groups.
Conclusions
Serum miR-210 and miR-1246 have some diagnostic value for discriminating patients with metastatic tumors to patients with primary HCC
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