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MicroRNA fingerprints identify miR-150 as a plasma prognostic marker in patients with sepsis
Catalin Vasilescu1, Simona Rossi, Masayoshi Shimizu
1Department of Surgery, Fundeni Clinical Hospital, Bucharest, Romania.
Background:
The 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 Findings:
By 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/Significance:
We 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.
Insights
MicroRNA-150 (miR-150) levels in blood can identify early sepsis and its severity. Reduced miR-150 correlates with sepsis progression, offering a potential diagnostic marker and therapeutic target.
Area of Science:
- Biochemistry
- Genetics
- Immunology
Background:
- Sepsis pathophysiology remains poorly understood, leading to high mortality despite treatment advances.
- Identifying novel diagnostic markers is crucial for developing targeted therapies and improving sepsis outcomes.
- MicroRNAs (miRNAs) are small regulatory RNAs implicated in various diseases, prompting investigation into their role in sepsis.
Purpose of the Study:
- To identify specific microRNAs (miRNAs) capable of distinguishing early-stage sepsis patients from healthy individuals.
- To assess the correlation between identified miRNA levels and sepsis severity, as measured by the Sequential Organ Failure Assessment (SOFA) score.
Main Methods:
- Genome-wide miRNA profiling using microarrays in peripheral blood leukocytes.
- Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) to validate miRNA expression in plasma.
- Correlation analysis of miRNA levels with SOFA scores and inflammatory cytokine levels (TNF-α, IL-10, IL-18).
Main Results:
- Expression profiles of miR-150, miR-182, miR-342-5p, and miR-486 differentiated sepsis patients from controls.
- miR-150 levels were significantly reduced in sepsis patient plasma and correlated negatively with SOFA scores, independent of white blood cell counts.
- Plasma levels of TNF-α, IL-10, and IL-18 were negatively correlated with miR-150 levels.
- The plasma miR-150/interleukin-18 ratio served as an indicator of sepsis severity.
Conclusions:
- Plasma and leukocyte miR-150 levels correlate with sepsis severity and can serve as an early sepsis diagnostic marker.
- Restoration of miR-150 is proposed as a potential future therapeutic strategy for sepsis patients.
