Usefulness of circulating microRNAs miR-146a and miR-16-5p as prognostic biomarkers in community-acquired pneumonia

PLoS One. 2020 Oct 23;15(10):e0240926. doi: 10.1371/journal.pone.0240926. eCollection 2020.

Abstract

Introduction: Patients with community-acquired pneumonia (CAP) undergo a dysregulated host response that is related to mortality. MicroRNAs (miRNAs) participate in this response, but their expression pattern and their role as biomarkers in CAP have not been fully characterized.

Methods: A prospective observational study was performed in a cohort of 153 consecutive patients admitted to hospital with CAP. Clinical and analytical variables were collected, and the main outcome variable was 30-day mortality. Small RNA was purified from plasma of these patients obtained on the first day of admission, and miRNA expression was analyzed by RT-PCR. Univariate and multivariate analyses were carried out through the construction of a logistic regression model. The proposed model was compared with established prognostic clinical scales using ROC curve analysis.

Results: The mean age of the patients included was 74.7 years [SD 15.9]. Their mean PSI was 100.9 [SD 34.6] and the mean modified Charlson index was 2.9 [SD 3.0]. Both miR-146a and miR-16-5p showed statistically significant association with 30-day mortality after admission due to CAP (1.10 vs. 0.23 and 51.74 vs. 35.23, respectively), and this association remained for miR-16-5p in the multivariate analysis adjusted for age, gender and history of bronchoaspiration (OR 0.95, p = 0.021). The area-under-the-curve (AUC) of our adjusted multivariate model (AUC = 0.954 95%CI [0.91-0.99]), was better than those of prognostic scales such as PSI (AUC = 0.799 [0.69-0.91]) and CURB-65 (AUC = 0.722 [0.58-0.86]).

Conclusions: High levels of miR-146a-5p and miR-16-5p upon admission due to CAP are associated with lower mortality at 30 days of follow-up. Both miRNAs could be used as biomarkers of good prognosis in subjects hospitalized with CAP.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Biomarkers / blood*
  • Community-Acquired Infections / blood
  • Community-Acquired Infections / genetics
  • Community-Acquired Infections / mortality*
  • Female
  • Hospitalization
  • Humans
  • Male
  • MicroRNAs / blood
  • MicroRNAs / genetics*
  • Middle Aged
  • Prognosis
  • Prospective Studies
  • Survival Analysis
  • Up-Regulation*

Substances

  • Biomarkers
  • MIRN146 microRNA, human
  • MIRN16 microRNA, human
  • MicroRNAs

Grants and funding

This work has been funded by the Carlos III Health Institute (ERDF, European Regional Development Fund), by the Spanish Society of Pneumology and Thoracic Surgery and by the Ministry of Science, Innovation and Universities of Spain. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.