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

Acute infections of the lower respiratory tract like community-acquired pneumonia (CAP) and acute exacerbations of chronic obstructive pulmonary disease (AECOPD) constitute the third most frequent cause of death worldwide. Urgent medical needs are early diagnosis and differential diagnosis as well as profound pathophysiological insights. Chronic obstructive pulmonary disease (COPD) is a poorly reversible condition characterized by airflow limitation and decrease of lung function. 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. We investigated the PBMC RNA profile of 5 healthy donors, 6 pneumonia patients and 6 COPD patients with acute exacerbations. From a total of 1,621 differentially expressed genes between CAP and AECOPD, we used Weighted Gene Co-expression Network Analysis (WGCNA) to extract a cluster of 120 genes (the module I) that exhibited the highest potency of disease type discrimination. We combined differentially regulated microRNAs and mRNAs into a regulatory network that functionally integrates the major distinctive factors between CAP and AECOPD. We identified the main hub molecule of this network, the transcription factor hepatocyte nuclear factor 4 alpha (HNF4A). Furthermore, other members of this network, such as MCC and MUC1, were found to be good discriminators between AECOPD and CAP. Likewise, we gathered several microRNAs, e.g. miR-545-3p and miR-519c-3p, which proved to be capable of separating AECOPD and CAP. The described RNA molecules may serve as accessible markers of disease in peripheral blood.