Serum microRNA signatures as "liquid biopsies" for interrogating hepatotoxic mechanisms and liver pathogenesis in human

by Julian Krauskopf, Theo M. de Kok, Shelli J. Schomaker, Mark Gosink, Deborah A. Burt, Patricia Chandler, Roscoe L. Warner, Kent J. Johnson, Florian Caiment, Jos C. Kleinjans, Jiri Aubrecht MicroRNAs (miRNAs) released into the peripheral circulation upon cellular injury have shown a promise as a new class of tissue-specific biomarkers. We were first to demonstrate that next-generation sequencing analysis of serum from human subjects with acetaminophen-induced liver injury revealed a specific signature of circulating miRNAs. We consequently hypothesized that different types of hepatic liver impairments might feature distinct signatures of circulating miRNAs and that this approach might be useful as minimally invasive diagnostic “liquid biopsies” enabling the interrogation of underlying molecular mechanisms of injury in distant tissues. Therefore we examined serum circulating miRNAs in a total of 72 serum samples from a group of 53 subjects that included patients with accidental acetaminophen overdose, hepatitis B infection, liver cirrhosis and type 2 diabetes as well a s gender- and age-matched healthy subjects with no evidence of liver disease. The miRNA signatures were identified using next-generation sequencing that provided analysis for the whole miRNome, including miRNA isoforms. Compared to the healthy subjects, a total of 179 miRNAs showed altered serum lev els across the diseased subjects. Although many subjects have elevated alanine aminotransferase suggesting l...
Source: PLoS One - Category: Biomedical Science Authors: Source Type: research