Evidence map›Paper›PMID 28545106›Full record

ArticlePloS one2017

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

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 and 1 more

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed, 1 pooled it
2.2field-weighted citation impact, top 12% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

27 citing papers in PubMed, 1 synthesis or guideline pooled it, 50 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Review
  4. Article
  5. Heliyon · 2024
    Article
  6. Article
  7. Review
  8. Article
  9. Review
  10. Exomeres and Supermeres: monolithic or diverse?Journal of extracellular biology · 2022
    Article
  11. Article
  12. Review
  13. Review
  14. Article
  15. Article
  16. Article
  17. Article
  18. Circulating microRNA Profiles in Acetaminophen Toxicity.Journal of medical toxicology : official journal of the American College of Medical Toxicology · 2020
    Observational
  19. Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors at 3 institutions in 2 countries.

Julian KrauskopfDepartment of Toxicogenomics, Maastricht University, Maastricht, the Netherlands.ORCID http://orcid.org/0000-0002-4349-9900
Theo M de KokDepartment of Toxicogenomics, Maastricht University, Maastricht, the Netherlands.
Shelli J SchomakerDrug Safety Research and Development, Pfizer Inc., Groton, Connecticut, United States of America.
Mark GosinkDrug Safety Research and Development, Pfizer Inc., Groton, Connecticut, United States of America.
Deborah A BurtDrug Safety Research and Development, Pfizer Inc., Groton, Connecticut, United States of America.
Patricia ChandlerClinical Research Unit, Pfizer Inc., New Haven, Connecticut, United States of America.
Roscoe L WarnerPathology Department, University of Michigan, Ann Arbor, Michigan, United States of America.
Kent J JohnsonPathology Department, University of Michigan, Ann Arbor, Michigan, United States of America.
Florian CaimentDepartment of Toxicogenomics, Maastricht University, Maastricht, the Netherlands.
Jos C KleinjansDepartment of Toxicogenomics, Maastricht University, Maastricht, the Netherlands.
Jiri AubrechtDrug Safety Research and Development, Pfizer Inc., Groton, Connecticut, United States of America.
Pfizer (United States) · USMaastricht University · NLUniversity of Michigan · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

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 as 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 levels across the diseased subjects. Although many subjects have elevated alanine aminotransferase suggesting liver impairments, we identified distinct miRNA signatures for different impairments with minimum overlap. Furthermore, the bioinformatics analysis of miRNA signatures revealed relevant molecular pathways associated with the mechanisms of toxicity and or pathogenesis of disease. Interestingly, the high proportion of miRNA isoforms present in the respective signatures indicated a new level of complexity in cellular response to stress or disease. Our study demonstrates for the first time that signatures of circulating miRNAs show specificity for liver injury phenotypes and, once validated, might become useful for diagnosis of organ pathologies as "liquid biopsies".

Indexed as

AdultBiomarkersChemical and Drug Induced Liver InjuryDiabetes Mellitus, Type 2FemaleGene Expression ProfilingGene Expression RegulationGene Regulatory NetworksGenetic Predisposition to DiseaseHepatitis BHigh-Throughput Nucleotide SequencingHumansLiver CirrhosisMaleMicroRNAsBiomarkersMicroRNAs

Identifiers

PMID28545106
PMCPMC5435338
OpenAlexW2616505961

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.