E-GEOD-28042 - Peripheral Blood Mononuclear Cell Gene Expression Profiles May Predict Poor Outcome in Idiopathic Pulmonary Fibrosis [Agilent]

Status
Released on 15 October 2013, last updated on 2 June 2014
Organism
Homo sapiens
Samples (94)
Array (1)
Protocols (7)
Description
Background: In this study we aimed to identify peripheral blood mononuclear cell (PBMC) gene expression profiles predictive of poor outcomes in idiopathic pulmonary fibrosis (IPF) Methods: Microarray analyses of PBMC were performed in 120 patients from discovery (n=45) and replication cohorts (n=75). Genes and pathways associated with transplant-free survival (TFS) were identified and confirmed by qRT-PCR. Findings: 52 genes were predictive of TFS in a discovery cohort (FDR<5%, Cox score above 2.5 or below -2.5). Clustering the replication cohort samples using these genes distinguished two patient groups with significantly different TFS (hazard ratio 1.96, 95%CI 1.01-3.8, P=0.018). Decreased expression of “The co-stimulatory signaling during T cell activation” Biocarta pathway and in particular CD28, ICOS, LCK and ITK was associated with shorter TFS times in each cohort (FDR<5%). qRT-PCR expression of CD28, ICOS, LCK and ITK correlated with the microarray results in the discovery cohort (P<0.05) and their decreased expression was predictive of shorter TFS in the replication cohort (P<0.05). A genomic and clinical model demonstrated an area under the ROC curve of 78.5% at 2.4 months for death and lung transplant prediction. Interpretation: Our results suggest that CD28, ICOS, LCK and ITK are outcome biomarkers in IPF. PBMC from 75 patients with the diagnosis of IPF were obtained within 30 minutes from blood draw. Total RNA was extracted, labeled and hybridized to Agilent Whole Human Genome Oligo Microarray, 4 x 44K. Patients were followed from blood draw until death, transplant or last follow up. Hierarchical clustering and gene-set analysis with censored outcome data were used to study the association of gene expression and outcome in this cohort (replication cohort)
Experiment type
transcription profiling by array 
Contacts
Citation
Peripheral blood mononuclear cell gene expression profiles predict poor outcome in idiopathic pulmonary fibrosis. Herazo-Maya JD, Noth I, Duncan SR, Kim S, Ma SF, Tseng GC, Feingold E, Juan-Guardela BM, Richards TJ, Lussier Y, Huang Y, Vij R, Lindell KO, Xue J, Gibson KF, Shapiro SD, Garcia JG, Kaminski N. , Europe PMC 24089408
MIAME
PlatformsProtocolsFactorsProcessedRaw
Files
Investigation descriptionE-GEOD-28042.idf.txt
Sample and data relationshipE-GEOD-28042.sdrf.txt
Raw data (2)E-GEOD-28042.raw.1.zip, E-GEOD-28042.raw.2.zip
Processed data (1)E-GEOD-28042.processed.1.zip
Array designA-AGIL-28.adf.txt
Links