Factors influencing circulating microRNAs as biomarkers for liver diseases

MicroRNAs (microRNAs) have been implicated to play crucial roles in various liver diseases. Hepatic microRNAs are released in to the circulation in a systematic fashion, and are, therefore, being extensively explored for their role as prognostic or diagnostic markers or therapeutic targets for numerous hepatic diseases. Advantages such as disease- or tissue-specific expression, and ease of detection have implicated circulating microRNAs (c-microRNAs) as the most desirable candidate for biomarker studies. Although several studies have explored c-microRNAs in serum or plasma, consistency of detection of microRNAs remains demanding because of many biological and methodological challenges. Lack of methodological consensus has limited the universal use of c-microRNAs as potential prognostic or diagnostic disease-specific biomarkers. In this review, we have discussed pre-analytical and analytical factors that might affect c-miRNA expression and selection of appropriate data normalization strategy by incorporating endogenous reference microRNAs. This review will aid designing of better approaches and protocols for future diagnostic research on hepatic c-microRNAs.