A critical evaluation of microRNA biomarkers in non-neoplastic disease. PLoS One 2014;9(2):e89565
Date
03/04/2014Pubmed ID
24586876Pubmed Central ID
PMC3935874DOI
10.1371/journal.pone.0089565Scopus ID
2-s2.0-84896277946 (requires institutional sign-in at Scopus site) 140 CitationsAbstract
BACKGROUND: MicroRNAs (miRNAs) are small (∼22-nt), stable RNAs that critically modulate post-transcriptional gene regulation. MicroRNAs can be found in the blood as components of serum, plasma and peripheral blood mononuclear cells (PBMCs). Many microRNAs have been reported to be specific biomarkers in a variety of non-neoplastic diseases. To date, no one has globally evaluated these proposed clinical biomarkers for general quality or disease specificity. We hypothesized that the cellular source of circulating microRNAs should correlate with cells involved in specific non-neoplastic disease processes. Appropriate cell expression data would inform on the quality and usefulness of each microRNA as a biomarker for specific diseases. We further hypothesized a useful clinical microRNA biomarker would have specificity to a single disease.
METHODS AND FINDINGS: We identified 416 microRNA biomarkers, of which 192 were unique, in 104 publications covering 57 diseases. One hundred and thirty-nine microRNAs (33%) represented biologically plausible biomarkers, corresponding to non-ubiquitous microRNAs expressed in disease-appropriate cell types. However, at a global level, many of these microRNAs were reported as "specific" biomarkers for two or more unrelated diseases with 6 microRNAs (miR-21, miR-16, miR-146a, miR-155, miR-126 and miR-223) being reported as biomarkers for 9 or more distinct diseases. Other biomarkers corresponded to common patterns of cellular injury, such as the liver-specific microRNA, miR-122, which was elevated in a disparate set of diseases that injure the liver primarily or secondarily including hepatitis B, hepatitis C, sepsis, and myocardial infarction.
CONCLUSIONS: Only a subset of reported blood-based microRNA biomarkers have specificity for a particular disease. The remainder of the reported non-neoplastic biomarkers are either biologically implausible, non-specific, or uninterpretable due to limitations of our current understanding of microRNA expression.
Author List
Haider BA, Baras AS, McCall MN, Hertel JA, Cornish TC, Halushka MKAuthor
Toby Charles Cornish MD, PhD Professor in the Pathology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Autoimmune DiseasesBiomarkers
Cardiovascular Diseases
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
Humans
Leukocytes, Mononuclear
Liver Diseases
Lung Diseases
MicroRNAs
Prognosis
