MicroRNA fingerprints identify miR-150 as a plasma prognostic marker in patients with sepsis.
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.


RESULTS
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
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.
Vasilescu
Catalin
C
Department of Surgery, Fundeni Clinical Hospital, Bucharest, Romania.
Rossi
Simona
S
Shimizu
Masayoshi
M
Tudor
Stefan
S
Veronese
Angelo
A
Ferracin
Manuela
M
Nicoloso
Milena S
MS
Barbarotto
Elisa
E
Popa
Monica
M
Stanciulea
Oana
O
Fernandez
Michael H
MH
Tulbure
Dan
D
Bueso-Ramos
Carlos E
CE
Negrini
Massimo
M
Calin
George A
GA
D000368:Aged; D005260:Female; D006801:Humans; D016753:Interleukin-10 / Q000097:blood; D020382:Interleukin-18 / Q000097:blood; D008297:Male; D035683:MicroRNAs / Q000097:blood* / Q000378:metabolism*; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D011446:Prospective Studies; D018805:Sepsis / Q000097:blood* / Q000382:microbiology* / Q000401:mortality; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D016753:Interleukin-10; D020382:Interleukin-18; D035683:MicroRNAs; D014409:Tumor Necrosis Factor-alpha; C533097:MIR150, human