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Veterinary and comparative oncology2018; 17(1); 107-117; doi: 10.1111/vco.12451

MicroRNA fingerprints in serum and whole blood of sarcoid-affected horses as potential non-invasive diagnostic biomarkers.

Abstract: Serum and whole blood microRNA (miRNA) fingerprints have been proposed as a new class of non-invasive human cancer biomarkers. In this study, we compared equine sarcoid (ES) disease-specific serum and whole blood miRNA fingerprints and correlated them to miRNA expression in sarcoid tissue. After high throughput sequencing, miRNA differential expression analysis between six ES-affected and five control horses was carried out in serum and whole blood using a DESeq algorithm, accounting for the influence of hemolysis and the white blood cell count. Target gene, pathway prediction and enrichment analyses were conducted using TarBase, mirPath and GeneCodis. After exclusion of 4 hemolyzed out of a total of 11 serum samples, 9 miRNAs were found to be differentially expressed in serum of ES vs control horses. In whole blood, all 11 samples showed normal white blood cell counts and 19 miRNAs were found to be differentially expressed. A total of 2/9 serum and 7/19 whole blood differentially expressed miRNAs were also highly expressed at the tissue level and their predicted target genes were associated with cancer pathways. Serum and whole blood miRNA expression allowed discrimination between ES and control horses and merits further validation in a larger study cohort. The use of whole blood might be superior because it has higher miRNA content and is less influenced by pre-analytical variables compared to serum. Concurrent dysregulation of single miRNAs in tissue and blood suggests a possible biological function of circulating miRNAs.
Publication Date: 2018-11-28 PubMed ID: 30430738DOI: 10.1111/vco.12451Google Scholar: Lookup
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  • Journal Article

Summary

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This study suggests that certain microRNA (miRNA) fingerprints found in horse blood and serum could be used as non-invasive biomarkers for equine sarcoid (ES), a type of skin tumor in horses. The differentiation of these miRNAs in ES-affected horses versus control ones was observed. Further, some of these miRNAs were linked to cancer pathways, providing potential diagnostic significance.

Research Methodology

  • The researchers compared miRNA fingerprints in the serum and whole blood of horses affected by ES to those in sarcoid tissue.
  • A differential expression analysis was performed using high throughput sequencing between six ES-affected horses and five controls in serum and whole blood. A DESeq algorithm helped to account for possible influence from hemolysis (breakdown of red blood cells) and white blood cell count.
  • This was followed by gene and pathway predictions and enrichment analyses performed via databases like TarBase, mirPath and GeneCodis.

Principal Findings

  • After excluding four samples marred by hemolysis, it was found that nine miRNAs were differentially expressed in the serum of ES-affected horses versus the controls. In whole blood, 19 miRNAs were demonstrably differently expressed between ES-affected and control horses. Of these, 2 out of the 9 serum miRNAs and 7 out of the 19 whole blood ones also showed high expression at the tissue level.
  • The target genes predicted for these highly expressed miRNAs were associated with cancer pathways.
  • This miRNA expression in serum and whole blood made it possible to distinguish between ES and control horses.

Conclusions and Implications

  • Given the favorable results, the study suggests that this investigative approach merits further validation with a larger study cohort.
  • Moreover, the use of whole blood appeared superior, as it contained higher miRNA content and was less influenced by pre-analytical variables compared to serum.
  • The concurrent dysregulation of single miRNAs in tissue and blood indicates a possible biological function of these circulating miRNAs, shedding light on the diagnostic potential of these miRNA ‘fingerprints’ for ES.

Cite This Article

APA
Unger L, Gerber V, Pacholewska A, Leeb T, Jagannathan V. (2018). MicroRNA fingerprints in serum and whole blood of sarcoid-affected horses as potential non-invasive diagnostic biomarkers. Vet Comp Oncol, 17(1), 107-117. https://doi.org/10.1111/vco.12451

Publication

ISSN: 1476-5829
NlmUniqueID: 101185242
Country: England
Language: English
Volume: 17
Issue: 1
Pages: 107-117

Researcher Affiliations

Unger, Lucia
  • Swiss Institute of Equine Medicine, Department of Clinical Veterinary Medicine, Vetsuisse Faculty, University of Bern, and Agroscope, Bern, Switzerland.
Gerber, Vinzenz
  • Swiss Institute of Equine Medicine, Department of Clinical Veterinary Medicine, Vetsuisse Faculty, University of Bern, and Agroscope, Bern, Switzerland.
Pacholewska, Alicja
  • Institute of Genetics, Vetsuisse Faculty, University of Bern, Bern, Switzerland.
Leeb, Tosso
  • Institute of Genetics, Vetsuisse Faculty, University of Bern, Bern, Switzerland.
Jagannathan, Vidhya
  • Institute of Genetics, Vetsuisse Faculty, University of Bern, Bern, Switzerland.

MeSH Terms

  • Animals
  • Biomarkers, Tumor / blood
  • Cohort Studies
  • Female
  • Gene Expression Regulation, Neoplastic
  • Horse Diseases / blood
  • Horse Diseases / diagnosis
  • Horses
  • Male
  • MicroRNAs / blood
  • MicroRNAs / metabolism
  • Skin Neoplasms / blood
  • Skin Neoplasms / diagnosis
  • Skin Neoplasms / veterinary

Grant Funding

  • Swiss Institute of Equine Medicine Research funds

Citations

This article has been cited 4 times.
  1. Hamza E, Cosandey J, Gerber V, Koch C, Unger L. The potential of three whole blood microRNAs to predict outcome and monitor treatment response in sarcoid-bearing equids.. Vet Res Commun 2023 Jan;47(1):87-98.
    doi: 10.1007/s11259-022-09930-7pubmed: 35484337google scholar: lookup
  2. Cosandey J, Hamza E, Gerber V, Ramseyer A, Leeb T, Jagannathan V, Blaszczyk K, Unger L. Diagnostic and prognostic potential of eight whole blood microRNAs for equine sarcoid disease.. PLoS One 2021;16(12):e0261076.
    doi: 10.1371/journal.pone.0261076pubmed: 34941894google scholar: lookup
  3. Unger L, Abril C, Gerber V, Jagannathan V, Koch C, Hamza E. Diagnostic potential of three serum microRNAs as biomarkers for equine sarcoid disease in horses and donkeys.. J Vet Intern Med 2021 Jan;35(1):610-619.
    doi: 10.1111/jvim.16027pubmed: 33415768google scholar: lookup
  4. Podstawski P, Witarski W, Szmatoła T, Bugno-Poniewierska M, Ropka-Molik K. Mobility and Invasion Related Gene Expression Patterns in Equine Sarcoid.. Animals (Basel) 2020 May 19;10(5).
    doi: 10.3390/ani10050880pubmed: 32438542google scholar: lookup