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MicroRNAs Could Serve as Biomarkers for Liver Impairment, Toxicity

NEW YORK (GenomeWeb) – A new study suggests that collections of microRNAs circulating in the blood may help to indicate the presence of underlying type 2 diabetes, or liver impairments ranging from liver cirrhosis to accidental acetaminophen overdose.

A team from the Netherlands and the US that included investigators from Pfizer Drug Safety Research and Development used small RNA sequencing to find miRNAs in blood serum samples from 53 individuals. In the process, the group identified miRNA clusters and signatures that appeared to coincide with each of the liver problems, pointing to potential approaches for finding, and understanding the biology of, various liver problems.

"Our work generates a foundation for potentially developing a non-invasive diagnostic screening test for liver pathology, capable of providing clinically relevant information regarding toxic effects of chemicals and the pathogenesis of diseases in the liver," wrote the authors of the study, published in PLOS One yesterday.

For their analyses, the researchers focused on 72 blood samples collected from 53 individuals at the University of Michigan — the group included 22 healthy control individuals, nine acetaminophen toxicity cases, eight individuals with alcohol-related liver cirrhosis, seven cases of hepatitis B virus, and seven individuals with type 2 diabetes.

Using Illumina HiSeq 2000 instruments, the team sequenced small RNAs  extracted from the blood serum samples and prepped for sequencing with a TruSeq small RNA kit.

In general, blood samples from individuals with liver problems had elevated miRNA levels compared to samples from their healthy counterparts, the researchers reported. Beyond that, they also saw differences in the particular miRNAs present in individuals affected by the varied liver conditions.

Nearly 80 percent of the blood miRNA repertoire was made up of the 10 main miRNAs in control individuals with healthy livers — an miRNA collection that appeared to remain relatively robust in samples from those with liver impairment. But the miRNAs identified in each condition also tended to cluster together, suggesting there might be liver injury clues that can be gleaned from blood samples.

In the individuals with accidental acetaminophen overdose, the researchers noted that miRNA clusters tended to creep closer to the patterns present in healthy control individuals over the course of a week, perhaps due to liver recovery after the acute liver assault.

When they delved into the particular miRNAs present in each liver impairment cluster, the investigators narrowed in on anywhere from 17 miRNAs in the individuals with alcohol-related liver cirrhosis to a 116- miRNA signature in the individuals with acetaminophen toxicity. And by looking at pathways expected to change in response to these miRNAs, they got a preliminary glimpse at the potential molecular alterations accompanying the liver impairments considered. 

"Compared to the healthy subjects, a total of 179 miRNAs showed altered serum levels across the diseased subjects," the authors wrote. "Our findings indicate the potential of miRNA signatures to be used as 'liquid biopsies,' thereby also providing mechanistic information relevant for cellular injury in distant tissues."