Gene expression profiling in blood of patients with chronic respiratory failure

Genes dysregulated in cystic fibrosis (CF) and primary pulmonary arterial hypertension (PAH) at a late stage of pulmonary failure are still largely unknown. Blood samples taken in the frame of the French cohort of lung transplantation COLT offers the opportunity to identify in blood specific gene signatures of each disease and a common gene signature for both pathologies. A microarray analysis was performed with homogeneous groups of CF patients (n=23), PAH (n=13) patients and healthy volunteers (n=28). Blood was collected in a PAXgene® tube to maintain RNA integrity. Total extracted RNA were processed on 60K whole-genome microarrays (Agilent Technologies). Microarrays were analyzed by bioinformatics (GOminer and Ingenuity Pathway Analysis). Three major biological signatures were discovered including (1) genes specifically over-expressed in pPAH and mainly involved in inflammation, vascular remodeling and cell proliferation, (2) genes specifically over-expressed in CF involved in innate immune response and oxidative stress response, and (3) genes under-expressed in both diseases, including genes involved in transcriptional machinery, apoptosis and cell proliferation. RNAs were isolated from blood collected with PAXGene tubes from 13 patients diagnosed with primitive pulmonary arterial hypertension (PAH), 23 patients with cystic fibrosis (CF) and 28 healthy volunteers (HVs).