The physiopathology of sepsis is still poorly understood and, despite recent advances in its management, this is a life threatening condition that represents the major cause of death among critically ill patients in Intensive Care Units (ICU). Therefore, there is a need for diagnostic markers related to pathogeny, useful for the development of new specific therapies. Since small non-coding RNAs named microRNAs (miRNAs) were recently linked to various human diseases, we aimed at the identification of miRNAs that could differentiate sepsis patients at early stages and eventually correlate with the ICU score. By genome-wide expression profiling in leukocytes and quantitative RT-PCR on plasma samples, we found that miR-150, miR-182, miR-342-5p and miR-486 expression could differentiate sepsis patients from healthy controls. In addition, we found that plasmatic level of miR-150 is significantly reduced in sepsis patients and correlates with the level of severity measured by the SOFA score. We also found that plasma levels of TNF-alpha, IL-10 and IL-18, genes with complementarity to miR-150 sequence, exhibited a negative correlation with plasma levels of this miRNA. Therefore, we propose that miR-150 levels in both leukocytes and plasma correlates with the aggressivity of sepsis after surgery and can be used as an early marker of sepsis.
Vasilescu C., Rossi S., Shimizu M., Tudor S., Veronese A., Ferracin M., et al. (2009). MicroRNA fingerprints identify miR-150 as a plasma prognostic marker in patients with sepsis. PLOS ONE, 4, 1-10 [10.1371/journal.pone.0007405].
MicroRNA fingerprints identify miR-150 as a plasma prognostic marker in patients with sepsis
FERRACIN, MANUELA;
2009
Abstract
The physiopathology of sepsis is still poorly understood and, despite recent advances in its management, this is a life threatening condition that represents the major cause of death among critically ill patients in Intensive Care Units (ICU). Therefore, there is a need for diagnostic markers related to pathogeny, useful for the development of new specific therapies. Since small non-coding RNAs named microRNAs (miRNAs) were recently linked to various human diseases, we aimed at the identification of miRNAs that could differentiate sepsis patients at early stages and eventually correlate with the ICU score. By genome-wide expression profiling in leukocytes and quantitative RT-PCR on plasma samples, we found that miR-150, miR-182, miR-342-5p and miR-486 expression could differentiate sepsis patients from healthy controls. In addition, we found that plasmatic level of miR-150 is significantly reduced in sepsis patients and correlates with the level of severity measured by the SOFA score. We also found that plasma levels of TNF-alpha, IL-10 and IL-18, genes with complementarity to miR-150 sequence, exhibited a negative correlation with plasma levels of this miRNA. Therefore, we propose that miR-150 levels in both leukocytes and plasma correlates with the aggressivity of sepsis after surgery and can be used as an early marker of sepsis.File | Dimensione | Formato | |
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2009_Vasilescu-PlosOne-150.pdf
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pone.0007405.s001.tif
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Descrizione: Figure S1: White blood count (WBC) and miR-150/miR-192 relative expression plot. No correlation was found in 23 sepsis samples (the WBC was missing for one sample) after standardization of miR-150 relative expression values and WBC values meaning that miR-150/miR-192 ratio is not just a biomarker for presence or absence of circulating leukocytes in sepsis. The standard values were derived by subtracting the mean of the relative expressions for miR-150 and miR-192 and mean of the WBC, respectively from each individual relative expression value and WBC value, respectively, and then dividing the difference by the standard deviation, calculated for each one of the data series.
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pone.0007405.s002.tif
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Descrizione: Figure S2: miR-150/miR-192 relative expression correlates with sepsis grade. The mean +/− standard deviation of miR-150/miR-192 fold difference related to sepsis grade (labeled as sepsis, SP, severe sepsis, SSP, and septic shock, SoP) is reported. As expected, miR-150 relative expression is higher in low sepsis grade samples (SP). P values were not statistically significant, probably due to the limited number of analyzed samples.
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