Blood Transcriptome Enriched with Megakaryocyte Gene Signature Predicts Poor Outcome in Idiopathic Pulmonary Fibrosis (IPF)
Year: 2021
Type: conference-abstract
Abstract: RATIONALE: A recent study in mice suggested that platelet-releasing megakaryocytes reside in lung interstitium and that the lung is a site of platelet biogenesis.The presence of magakaryocytes in the lungs have also been reported in human.However, the role of megakaryocytes and platelets in idiopathic pulmonary fibrosis (IPF) is illdefined.We sought to investigate whether megakaryocyte/platelet gene signature is altered in lung and/or blood transcriptome in IPF.METHODS: Lung and blood transcriptome data of IPF patients and their controls in the NCBI Gene Expression Omnibus (GEO) repository were analyzed (GSE47460, GSE93606).Enrichment of magakaryocytes and platelets in IPF and the control were estimated using xCell, a novel computational method that assesses enrichment of individual cell types based on gene expression profile.We first compared enrichment scores for each cell type in IPF and the control, using t-test or Mann-Whitney U test.With regard to blood transcriptome of IPF patients, we also compared the disease progression-free survival (i.e., survival without significant [>10%] decline in forced lung capacity [FVC]) over 6 months, between patients with high megakaryocyte enrichment score and patients with low megakaryocyte enrichment score, using log-rank test.A p-value <0.05 was considered statistically significant.RESULTS: In the lung transcriptome data, a megakaryocyte gene signature was less enriched in IPF than in the control group.On the other hand, in the blood transcriptome, a megakaryocyte gene signature was more enriched in IPF than in the control group.Moreover, IPF patients with higher megakaryocyte score (above median) in blood transcriptome had worse disease progression-free survival than IPF patients with lower megakaryocyte score (below median) (log rank test p=0.0096).There was no significant difference in platelet enrichment scores between IPF and the control in lung or blood.CONCLUSION: In IPF, a megakaryocyte gene signature is altered in the lung and blood transcriptome.Moreover, the blood transcriptome enriched with the megakaryocyte gene signature predicts poor outcome in IPF.These data suggest that a megakaryocyte gene signature in peripheral blood may be a novel biomarker in IPF.
Institution: Tulane University
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
OpenAlex ID: W4240808394