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

Abstract

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. Community acquired pneumonia (CAP) is clinically defined by a sudden onset of severe illness that is accompanied by signs of lower respiratory tract infection, fever, cough and dyspnoea 1. When left untreated, severe secondary effects such as organ damage and occurrence of bacteria in the blood (bacteremia) can ensue. While subject to variance due to region, season and population characteristics, the incidence of CAP is estimated to lie between 1.5 and 14 cases per 1,000 persons per year, with children under 5 years of age and the elderly of more than 65 years being most strongly affected 2. Immunocompromised persons also bear a higher risk of CAP contraction. The leading underlying cause of CAP is infection with the gram-positive bacterium Streptococcus pneumoniae, accounting for 30-35% of CAP cases worldwide 3. The initial colonization of the nasopharynx and the upper respiratory tract often remains asymptomatic. Aspiration into the alveoli can cause severe respiratory or systemic disease, depending on the host immune status and the pneumococcal serotype 1. As CAP is a multifaceted disease with a host of potential causative agents, the robust identification of microR-NAs that are functionally involved in pneumonia depends on the pathogen. In severe Influenza A Virus (H1N1)

MicroRNAs as Potential Regulators of Immune Response Networks in Asthma and Chronic Obstructive Pulmonary Disease

“…Plasma miRNAs can be used to identify patients with acute exacerbations of COPD such as miR-125b ( 105 ). PBMC-derived miRNAs are also differentially expressed in acute exacerbations of COPD compared to stable COPD and can differentiate between both conditions ( 129 ).…”

A review of miRNAs accuracy as a diagnostic biomarker in COPD patients

“…Classification approach using 120 genes (including mRNA and miRNA) was able to distinguish the two groups with an AUC of 0.861. 13 A study by Asensio et al reported different expression profiles of eosinophilic COPD from smoking asthmatic, nonsmoking asthmatic and non-eosinophilic COPD patients. A preliminary analysis of 40 peripheral blood serum samples reported consistent significant difference of miR-619-5p and miR-4486 expression in eosinophilic COPD patients compared to others.…”

Non-Coding RNAs and SARS-Related Coronaviruses

“…miRNAs can be used as biomarkers for the diagnosis of certain infectious diseases, e.g., miR-519c-3p serves as a biomarker to distinguish community-acquired pneumonia from chronic obstructive pulmonary disease exacerbations [49]. Guterres et al [50] suggest that miRNAs may also be used as biomarkers for the determination of the disease progression of COVID-19.…”