title: The peripheral blood transcriptome identifies the presence and extent of disease in idiopathic pulmonary fibrosis.
abstract: BACKGROUND
  Peripheral blood biomarkers are needed to identify and determine the extent of idiopathic pulmonary fibrosis (IPF). Current physiologic and radiographic prognostic indicators diagnose IPF too late in the course of disease. We hypothesize that peripheral blood biomarkers will identify disease in its early stages, and facilitate monitoring for disease progression.
  
  
  METHODS
  Gene expression profiles of peripheral blood RNA from 130 IPF patients were collected on Agilent microarrays. Significance analysis of microarrays (SAM) with a false discovery rate (FDR) of 1% was utilized to identify genes that were differentially-expressed in samples categorized based on percent predicted D(L)CO and FVC.
  
  
  RESULTS
  At 1% FDR, 1428 genes were differentially-expressed in mild IPF (D(L)CO >65%) compared to controls and 2790 transcripts were differentially- expressed in severe IPF (D(L)CO >35%) compared to controls. When categorized by percent predicted D(L)CO, SAM demonstrated 13 differentially-expressed transcripts between mild and severe IPF (< 5% FDR). These include CAMP, CEACAM6, CTSG, DEFA3 and A4, OLFM4, HLTF, PACSIN1, GABBR1, IGHM, and 3 unknown genes. Principal component analysis (PCA) was performed to determine outliers based on severity of disease, and demonstrated 1 mild case to be clinically misclassified as a severe case of IPF. No differentially-expressed transcripts were identified between mild and severe IPF when categorized by percent predicted FVC.
  
  
  CONCLUSIONS
  These results demonstrate that the peripheral blood transcriptome has the potential to distinguish normal individuals from patients with IPF, as well as extent of disease when samples were classified by percent predicted D(L)CO, but not FVC.
authors: Center for Genes, Environment and Health, National Jewish Health, Denver, Colorado, United States of America.
authors: Ivana V
authors: IV
authors: Yang
authors: Leah G
authors: LG
authors: Luna
authors: Jennifer
authors: J
authors: Cotter
authors: Janet
authors: J
authors: Talbert
authors: Sonia M
authors: SM
authors: Leach
authors: Raven
authors: R
authors: Kidd
authors: Julia
authors: J
authors: Turner
authors: Nathan
authors: N
authors: Kummer
authors: Dolly
authors: D
authors: Kervitsky
authors: Kevin K
authors: KK
authors: Brown
authors: Kathy
authors: K
authors: Boon
authors: Marvin I
authors: MI
authors: Schwarz
authors: David A
authors: DA
authors: Schwartz
authors: Mark P
authors: MP
authors: Steele
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood*; D002248:Carbon Monoxide / Q000378:metabolism; D016022:Case-Control Studies; D018450:Disease Progression; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D054988:Idiopathic Interstitial Pneumonias / Q000097:blood / Q000175:diagnosis* / Q000235:genetics; D054990:Idiopathic Pulmonary Fibrosis / Q000097:blood / Q000175:diagnosis* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014797:Vital Capacity
chemical_list: D015415:Biomarkers; D012333:RNA, Messenger; D002248:Carbon Monoxide