Abstract

Introduction Alterations in miR-155 serum levels have been described in inflammatory and infectious diseases. Moreover, a role for miR-155 in aging and age-related diseases was recently suggested. We therefore analyzed a potential age-dependent prognostic value of circulating miR-155 as a serum-based marker in critical illness. Methods Concentrations of circulating miR-155 were determined in 218 critically ill patients and 76 healthy controls. Results By using qPCR, we demonstrate that miR-155 serum levels are elevated in patients with critical illness when compared to controls. Notably, levels of circulating miR-155 were independent on the severity of disease, the disease etiology, or the presence of sepsis. In the total cohort, miR-155 was not an indicator for patient survival. Intriguingly, when patients were subdivided according to their age upon admission to the ICU into those younger than 65 years, lower levels of miR-155 turned out as a strong marker, indicating patient mortality with a similar accuracy than other markers frequently used to evaluate critically ill patients on a medical ICU. Conclusion In summary, the data provided within this study suggest an age-specific role of miR-155 as a prognostic biomarker in patients younger than 65 years. Our study is the first to describe an age-dependent miRNA-based prognostic biomarker in human diseases.

Highlights

  • Alterations in miR-155 serum levels have been described in inflammatory and infectious diseases

  • Our study reports a novel role of circulating miR-155 in distinguishing critically ill patients from healthy controls and in predicting survival of critically ill patients < 65 years old

  • A Chinese study group investigated a cohort of sixty patients and found that, compared to healthy controls, sepsis patients exhibit significantly elevated miR-155 levels, which is positively related to a greater severity of sepsis [20]

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Summary

Introduction

Sepsis represents a complex pathological process including inflammation, coagulopathy, and deterioration of the patients’ hemodynamic state, leading to organ failure [1]. MicroRNAs represent endogenous RNA molecules with a length of ~22 nucleotides [5] They are created by a complex process leading from pre-miRNAs to the mature miRNA that regulates multiple processes such as cell metabolism, cell growth, and differentiation as well as cell death [5]. In a recently published in vitro study using LPS-induced THP-1 monocytes, it was demonstrated that miR-155 regulated the expression of different proinflammatory mediators [14], arguing for a function in systemic inflammation and infection Due to their simple chemical structure and the resulting biological stability, circulating miRNAs were proposed by many authors as biomarkers for several diseases including. We analyzed the diagnostic and prognostic value of miR-155 serum levels in 218 critically ill patients treated on an intensive care unit

Methods
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