Abstract:
Hepatitis C virus (HCV) infection is a serious health challenge affecting over
185 million individuals globally. Egypt has the highest rate for chronic HCV infection
worldwide. Recent studies have shown that from 10%-30% of HCV infected
individuals would progress to more deteriorating conditions such as cirrhosis and/or
hepatocellular carcinoma (HCC). Current biomarkers for HCC diagnosis are lacking
both sensitivity and specificity. As a result there is demand to develop reliable
biomarkers that are sensitive, specific and non-invasive for early diagnosis and rapid
intervention of HCC to increase the survival rate of patients. Recently, circulatory miRNAs
have drawn great attention as promising non-invasive biomarkers for various
diseases. They are highly stable in blood and their expression profiles reflect disease
progression and/or drug response status. Besides, a number of miRNAs were found to
be commonly dysregulated in HCC.
In this study, we investigated mi-RNA expression profile from the plasma of
Egyptian patients with chronic hepatitis C, cirrhosis and HCV associated HCC
compared with healthy control. We aimed to assess the diagnostic potential of the
selected miRNAs to differentiate between healthy, HCV and HCV associated
disorders (cirrhosis and HCC). In addition to studying the expression pattern in the
different studied stages.
Using real time PCR, we compared the levels of circulating mir-122, miR-21
and miR-155 in plasma from healthy control (n=40), cirrhosis (n=39) and HCC
(n=40) to CHC (n=37). Synthetic miR-39 was spiked in the samples to be used as a
normalizing control for the samples. Plasma miR-122 was significantly up-regulated
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in HCC than in the three other categories (P<0.001). The plasma level of miR-122 in
HCC patients was significantly higher than healthy control and cirrhotic patients (P =
0.002 and P<0.001, respectively). The plasma level of miR-21 was significantly upregulated
in HCC compared to cirrhotic patients (P=0.03). Although Control and
HCC in mir-21 increased by 3.52 and 6 log2 scale respectively, they were in marginal
insignificance (p=0.093) that might be due to limited number of samples used in this
study. There had been no significant dys-regulation in the expression levels of miR155
between the 4 categories.
Receiver operating characteristic curves’ analysis revealed that miR-122
differentiated HCC patients from healthy control with a specificity and sensitivity
57.50% and 65.52% respectively (at a cutoff >1.86). To discriminate cirrhotic patients
from HCC subjects, a specificity and sensitivity of 61.54% and 1.43% (at a cutoff>
0.43) were determined. Additionally, analyzing ROC curve indicated that miR-21
differentiated HCC patients from cirrhotic patients with best sensitivity and specificity
72.97% and 50% (at a cutoff >-0.43).
In conclusion, plasma miR-122 and miR-21 may be further investigated as
potential markers for HCV associated HCC.