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Published on: October 26, 2017
Diagnostic potential of circulating cell-free microRNAs for community-acquired pneumonia and pneumonia-related sepsis
Stefanie Hermann1, Florian Brandes2, Benedikt Kirchner1
1Division of Animal Physiology and Immunology, School of Life Sciences Weihenstephan, Technical University of Munich, Freising, Germany.
Abstract:
Cell-free microRNAs (miRNAs) are transferred in disease state including inflammatory lung diseases and are often packed into extracellular vesicles (EVs). To assess their suitability as biomarkers for community-acquired pneumonia (CAP) and severe secondary complications such as sepsis, we studied patients with CAP (n = 30), sepsis (n = 65) and healthy volunteers (n = 47) subdivided into a training (n = 67) and a validation (n = 75) cohort. After precipitating crude EVs from sera, associated small RNA was profiled by next-generation sequencing (NGS) and evaluated in multivariate analyses. A subset of the thereby identified biomarker candidates was validated both technically and additionally by reverse transcription quantitative real-time PCR (RT-qPCR). Differential gene expression (DGE) analysis revealed 29 differentially expressed miRNAs in CAP patients when compared to volunteers, and 25 miRNAs in patients with CAP, compared to those with sepsis. Sparse partial-least discriminant analysis separated groups based on 12 miRNAs. Three miRNAs proved as a significant biomarker signature. While expression levels of miR-1246 showed significant changes with an increase in overall disease severity from volunteers to CAP and to sepsis, miR-193a-5p and miR-542-3p differentiated patients with an infectious disease (CAP or sepsis) from volunteers. Cell-free miRNAs are potentially novel biomarkers for CAP and may help to identify patients at risk for progress to sepsis, facilitating early intervention and treatment.
Insights
Cell-free microRNAs (miRNAs) in extracellular vesicles show promise as biomarkers for community-acquired pneumonia (CAP) and sepsis. These findings could aid in early detection and intervention for patients at risk of severe complications.
Area of Science:
- Biochemistry
- Molecular Biology
- Genomics
Background:
- Cell-free microRNAs (miRNAs) are implicated in disease pathogenesis and can be packaged into extracellular vesicles (EVs).
- Investigating circulating miRNAs as biomarkers for inflammatory lung diseases like community-acquired pneumonia (CAP) and sepsis is crucial for early diagnosis and treatment.
Purpose of the Study:
- To evaluate the potential of cell-free miRNAs within EVs as diagnostic biomarkers for CAP and sepsis.
- To identify specific miRNA signatures that can differentiate between healthy individuals, CAP patients, and sepsis patients.
Main Methods:
- Serum extracellular vesicles (EVs) were isolated from healthy volunteers, CAP patients, and sepsis patients.
- Small RNA profiling was performed using next-generation sequencing (NGS), followed by multivariate analysis.
- Candidate biomarker miRNAs were validated using reverse transcription quantitative real-time PCR (RT-qPCR).
Main Results:
- Differential gene expression analysis identified 29 differentially expressed miRNAs in CAP versus volunteers and 25 in CAP versus sepsis.
- A signature of 12 miRNAs was identified using sparse partial least discriminant analysis.
- Three miRNAs (miR-1246, miR-193a-5p, and miR-542-3p) emerged as significant biomarkers, with miR-1246 correlating with disease severity.
Conclusions:
- Cell-free miRNAs encapsulated in EVs represent potential novel biomarkers for CAP.
- These miRNA biomarkers may facilitate the early identification of patients progressing to sepsis, enabling timely therapeutic interventions.

