Transcriptional analysis identifies potential biomarkers and molecular regulators in pneumonia and COPD exacerbation

Lower respiratory infections, such as community-acquired pneumonia (CAP), and chronic obstructive pulmonary disease (COPD) rank among the most frequent causes of death worldwide. Improved diagnostics and profound pathophysiological insights are urgent clinical needs. In our cohort, we analysed trans...

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Published in:Scientific reports 2020-01, Vol.10 (1), p.241-241, Article 241
Main Authors: Bertrams, Wilhelm, Griss, Kathrin, Han, Maria, Seidel, Kerstin, Klemmer, Andreas, Sittka-Stark, Alexandra, Hippenstiel, Stefan, Suttorp, Norbert, Finkernagel, Florian, Wilhelm, Jochen, Greulich, Timm, Vogelmeier, Claus F, Vera, Julio, Schmeck, Bernd
Format: Article
Language:English
Subjects:
Biomarkers
Biomarkers - metabolism
Chronic obstructive pulmonary disease
Community-Acquired Infections - genetics
Computational Biology
DNA microarrays
Female
Gene expression
Gene Expression Profiling
Hepatocyte nuclear factor 4
Humans
Leukocytes (mononuclear)
Lung diseases
Male
MicroRNAs
MicroRNAs - genetics
miRNA
Obstructive lung disease
Peripheral blood mononuclear cells
Pneumonia
Pneumonia - genetics
Pulmonary Disease, Chronic Obstructive - genetics
Tissue Donors
Transcription
Transcription, Genetic
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Summary:Lower respiratory infections, such as community-acquired pneumonia (CAP), and chronic obstructive pulmonary disease (COPD) rank among the most frequent causes of death worldwide. Improved diagnostics and profound pathophysiological insights are urgent clinical needs. In our cohort, we analysed transcriptional networks of peripheral blood mononuclear cells (PBMCs) to identify central regulators and potential biomarkers. We investigated the mRNA- and miRNA-transcriptome of PBMCs of healthy subjects and patients suffering from CAP or AECOPD by microarray and Taqman Low Density Array. Genes that correlated with PBMC composition were eliminated, and remaining differentially expressed genes were grouped into modules. One selected module (120 genes) was particularly suitable to discriminate AECOPD and CAP and most notably contained a subset of five biologically relevant mRNAs that differentiated between CAP and AECOPD with an AUC of 86.1%. Likewise, we identified several microRNAs, e.g. miR-545-3p and miR-519c-3p, which separated AECOPD and CAP. We furthermore retrieved an integrated network of differentially regulated mRNAs and microRNAs and identified HNF4A, MCC and MUC1 as central network regulators or most important discriminatory markers. In summary, transcriptional analysis retrieved potential biomarkers and central molecular features of CAP and AECOPD.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-019-57108-0