Comprehensive miRNA Expression Analysis in Peripheral Blood Can Diagnose Liver Disease

Abstract

BackgroundmiRNAs circulating in the blood in a cell-free form have been acknowledged for their potential as readily accessible disease markers. Presently, histological examination is the golden standard for diagnosing and grading liver disease, therefore non-invasive options are desirable. Here, we investigated if miRNA expression profile in exosome rich fractionated serum could be useful for determining the disease parameters in patients with chronic hepatitis C (CHC).MethodologyExosome rich fractionated RNA was extracted from the serum of 64 CHC and 24 controls with normal liver (NL). Extracted RNA was subjected to miRNA profiling by microarray and real-time qPCR analysis. The miRNA expression profiles from 4 chronic hepatitis B (CHB) and 12 non alcoholic steatohepatitis (NASH) patients were also established. The resulting miRNA expression was compared to the stage or grade of CHC determined by blood examination and histological inspection.Principal FindingsmiRNAs implicated in chronic liver disease and inflammation showed expression profiles that differed from those in NL and varied among the types and grades of liver diseases. Using the expression patterns of nine miRNAs, we classified CHC and NL with 96.59% accuracy. Additionally, we could link miRNA expression pattern with liver fibrosis stage and grade of liver inflammation in CHC. In particular, the miRNA expression pattern for early fibrotic stage differed greatly from that observed in high inflammation grades.ConclusionsWe demonstrated that miRNA expression pattern in exosome rich fractionated serum shows a high potential as a biomarker for diagnosing the grade and stage of liver diseases.

MicroRNAs for the Prediction of Early Response to Sorafenib Treatment in Human Hepatocellular Carcinoma

“…So far, a number of studies have shown the role of miRNAs in the pathogenesis of liver disease including HCC [19]. Moreover, miRNAs detected in circulating blood are usually present within microvesicles such as exosomes [20,21]; the circulating miRNAs could be markers of HCC progression [22]. However, it is difficult to evaluate the serum miRNA profiles from cancer cells for several reasons.…”

The chronic enteropathogenic disease schistosomiasis

“…The expression levels of two miRNAs (miR-483-5p and miR-671-5p) increased significantly and the expression levels of 14 miRNAs (let7a, miR-106b, miR-1274a, miR-130b, miR-140-3p, miR-151-3p, miR-181a, miR-19b, miR-21, miR-24, miR-375, miR-548l, miR-93, and miR-941) were progressively reduced as liver fibrosis increased. 116 As schistosomal egg-induced immunopathology is an unusual type of chronic liver disease distinguishable from many other liver disease types, it is tempting to speculate that a unique set of circulating miRNAs may be defined to potentially serve as sensitive molecular signatures for assessment of the severity of the fibrotic pathology of schistosomiasis. To date, a set of miRNAs of parasite origin have been identified in both S. japonicum 117,118 and S. mansoni 119,120 and miRNA expression profiles at different developmental stages of S. japonicum have been characterized.…”

Current status of fibrosis markers

“…An interesting study evaluated miRNA expression in exosome-rich fractionated serum in 64 CHC and 12 NASH patients, and was able to differentiate both CHC from NASH and stage F0 from F1-3 with an accuracy of 87% [38]. Further studies to demonstrate diagnostic and prognostic utility of miRNAs as biomarkers in CLD are needed.…”