MicroRNA Fingerprints Identify miR-150 as a Plasma Prognostic Marker in Patients with Sepsis

Abstract

BackgroundThe physiopathology of sepsis continues to be poorly understood, and despite recent advances in its management, sepsis is still a life-threatening condition with a poor outcome. If new diagnostic markers related to sepsis pathogenesis will be identified, new specific therapies might be developed and mortality reduced. Small regulatory non-coding RNAs, microRNAs (miRNAs), were recently linked to various diseases; the aim of our prospective study was to identify miRNAs that can differentiate patients with early-stage sepsis from healthy controls and to determine if miRNA levels correlate with the severity assessed by the Sequential Organ Failure Assessment (SOFA) score.Methodology/Principal FindingsBy using genome-wide miRNA profiling by microarray in peripheral blood leukocytes, we found that miR-150, miR-182, miR-342-5p, and miR-486 expression profiles differentiated sepsis patients from healthy controls. We also proved by quantitative reverse transcription-polymerase chain reaction that miR-150 levels were significantly reduced in plasma samples of sepsis patients and correlated with the level of disease severity measured by the SOFA score, but were independent of the white blood counts (WBC). We found that plasma levels of tumor necrosis factor alpha, interleukin-10, and interleukin-18, all genes with sequence complementarity to miR-150, were negatively correlated with the plasma levels of this miRNA. Furthermore, we identified that the plasma levels ratio for miR-150/interleukin-18 can be used for assessing the severity of the sepsis.Conclusions/SignificanceWe propose that miR-150 levels in both leukocytes and plasma correlate with the aggressiveness of sepsis and can be used as a marker of early sepsis. Furthermore, we envision miR-150 restoration as a future therapeutic option in sepsis patients.

Evaluation of serum extracellular vesicle isolation methods for profiling miRNAs by next‐generation sequencing

“…In mice and rats, miR-150-5p, upregulated in samples captured by membrane affinity, was increased by polymicrobial sepsis and LPS treatment, respectively [60,61]. Vasilescu et al reported plasma levels of miR-150-5p to correlate with sepsis aggressiveness in a cohort of 17 sepsis patients [62]. In concordance with previous findings in critically ill patients, we detected miR-122-5p as upregulated in samples derived from all isolation methods.…”

Small RNAs have a large impact

“…Candidate miRNAs from the profiles were miR-150, miR-182, miR-342-5p, miR-486 and miR-132, miR-146a, miR-155 and miR-223. Plasma levels of miR-150 decreased significantly 53 while serum miR-146a and miR-223 were significantly reduced in septic patients compared with controls. 54 Not only are new biomarkers for determining the severity of the condition important, new biomarkers are also needed in the search for septic treatment.…”

“…Detection methods need adjustment to minimize protocol-based bias, and the strategy of raw data normalization is a critical issue. So far, several normalization strategies for the analysis of circulating miRNAs are available, such as using literature-based tissue housekeeping genes or miRNAs as normalizers, 28,32,37,53,56 which has been challenged by the fact of unstable expression of these "tissue normalizers" in serum. 15,19,57 Normalizing serum miRNA expression by using equal amounts of serum across all samples has also been adopted, which may be insufficient as our lab and others have noticed the considerable variations in RNA quantities extracted from equal volumes of serum from different individuals.…”

Patients After Splenectomy: Old Risks and New Perspectives

“…Our group observed in plasma of septic patients, that miR-150 is significantly downregulated and that its value correlates with the aggressiveness of the disease. We proposed miR-150 as a new biomarker for sepsis (51). In a recent study, Tudor et al found 12 deregulated miRNAs in plasma of septic patients.…”