title: MicroRNA fingerprints identify miR-150 as a plasma prognostic marker in patients with sepsis.
abstract: 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.
authors.affiliation: Department of Surgery, Fundeni Clinical Hospital, Bucharest, Romania.
authors.forename: Catalin
authors.initials: C
authors.lastname: Vasilescu
authors.forename: Simona
authors.initials: S
authors.lastname: Rossi
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Shimizu
authors.forename: Stefan
authors.initials: S
authors.lastname: Tudor
authors.forename: Angelo
authors.initials: A
authors.lastname: Veronese
authors.forename: Manuela
authors.initials: M
authors.lastname: Ferracin
authors.forename: Milena S
authors.initials: MS
authors.lastname: Nicoloso
authors.forename: Elisa
authors.initials: E
authors.lastname: Barbarotto
authors.forename: Monica
authors.initials: M
authors.lastname: Popa
authors.forename: Oana
authors.initials: O
authors.lastname: Stanciulea
authors.forename: Michael H
authors.initials: MH
authors.lastname: Fernandez
authors.forename: Dan
authors.initials: D
authors.lastname: Tulbure
authors.forename: Carlos E
authors.initials: CE
authors.lastname: Bueso-Ramos
authors.forename: Massimo
authors.initials: M
authors.lastname: Negrini
authors.forename: George A
authors.initials: GA
authors.lastname: Calin
mesh_terms: 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
chemical_list: D016753:Interleukin-10; D020382:Interleukin-18; D035683:MicroRNAs; D014409:Tumor Necrosis Factor-alpha; C533097:MIR150, human