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Genome-Wide Sequencing of Cellular microRNAs Identifies a Combinatorial Expression Signature Diagnostic of Sepsis

Research output: Contribution to journalArticle

Yuqian Ma, David Vilanova, Kerem Atalar, Olivier Delfour, Jonathan Edgeworth, Marlies Ostermann, Maria Hernandez Fuentes, Sandrine Razafimahatratra, Bernard Michot, David H Persing, Ingrid Ziegler, Bianca Törös, Paula Mölling, Per Olcén, Richard Beale, Graham M Lord

Original languageEnglish
Article numbere75918
Number of pages12
JournalPLoS ONE
Volume8
Issue number10
DOIs
Publication statusPublished - 16 Oct 2013

Documents

  • journal.pone.0075918

    journal.pone.0075918.pdf, 1.58 MB, application/pdf

    4/01/2016

    Final published version

    CC BY

King's Authors

Abstract

Rationale

Sepsis is a common cause of death in the intensive care unit with mortality up to 70% when accompanied by multiple organ dysfunction. Rapid diagnosis and the institution of appropriate antibiotic therapy and pressor support are therefore critical for survival. MicroRNAs are small non-coding RNAs that play an important role in the regulation of numerous cellular processes, including inflammation and immunity.

Objectives

We hypothesized changes in expression of microRNAs during sepsis may be of diagnostic value in the intensive care unit (ICU).

Methods

Massively parallel sequencing of microRNAs was utilised for screening microRNA candidates. Putative microRNAs were validated using quantitative real-time PCR (qRT-PCR). This study includes data from both a training cohort (UK) and an independent validation cohort (Sweden). A linear discriminant statistical model was employed to construct a diagnostic microRNA signature.

Results

A panel of known and novel microRNAs were detectable in the blood of patients with sepsis. After qRT-PCR validation, microRNA miR-150 and miR-4772-5p-iso were able to discriminate between patients who have systemic inflammatory response syndrome and patients with sepsis. This finding was also validated in independent cohort with an average diagnostic accuracy of 86%. Fractionating the cellular components of blood reveals miR-4772-5p-iso is expressed differentially in monocytes. Functional experiments using primary human monocytes demonstrate that it expressed in response to TLR ligation.

Conclusions

Taken together, these data provide a novel microRNA signature of sepsis that should allow rapid point-of-care diagnostic assessment of patients on ICU and also provide greater insight into the pathobiology of this severe disease.

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