title: Whole blood biomarkers of acute cardiac allograft rejection: double-crossing the biopsy.
abstract: BACKGROUND
  Acute rejection is still a significant barrier to long-term survival of the allograft. Current acute rejection diagnostic methods are not specific enough or are invasive. There have been a number of studies that have explored the blood or the biopsy to discover genomic biomarkers of acute rejection; however, none of the studies to date have used both.
  
  
  METHODS
  We analyzed endomyocardial biopsy tissue and whole blood-derived messenger RNA from 11 acute rejection and 20 nonrejection patients using Affymetrix Human Genome U133 Plus 2.0 chips. We used a novel approach and gained insight into the biology of rejection based on gene expression in the biopsy, and applied this knowledge to the blood analysis to identify novel blood biomarkers.
  
  
  RESULTS
  We identified probesets that are differentially expressed between acute rejection and nonrejection patients in the biopsy and blood, and developed three biomarker panels: (1) based on biopsy-only (area under the curve=0.85), (2) based on biopsy-targeted whole blood (area under the curve=0.83), and (3) based on whole blood-only (area under the curve=0.60) analyses.
  
  
  CONCLUSIONS
  Most of the probesets replicated between biopsy and blood are regulated in opposite direction between the two sources of information. We also observed that the biopsy-targeted blood biomarker discovery approach can improve performance of the biomarker panel. The biomarker panel developed using this targeted approach is able to diagnose acute cardiac allograft rejection almost as well as the biopsy-only based biomarker panel.
authors.affiliation: NCE CECR PROOF Centre of Excellence, Vancouver, BC, Canada.
authors.forename: Zsuzsanna
authors.initials: Z
authors.lastname: Hollander
authors.forename: David
authors.initials: D
authors.lastname: Lin
authors.forename: Virginia
authors.initials: V
authors.lastname: Chen
authors.forename: Raymond
authors.initials: R
authors.lastname: Ng
authors.forename: Janet
authors.initials: J
authors.lastname: Wilson-McManus
authors.forename: Andrew
authors.initials: A
authors.lastname: Ignaszewski
authors.forename: Gabriela
authors.initials: G
authors.lastname: Cohen Freue
authors.forename: Rob
authors.initials: R
authors.lastname: Balshaw
authors.forename: Alice
authors.initials: A
authors.lastname: Mui
authors.forename: Robert
authors.initials: R
authors.lastname: McMaster
authors.forename: Paul A
authors.initials: PA
authors.lastname: Keown
authors.forename: Bruce M
authors.initials: BM
authors.lastname: McManus
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D019540:Area Under Curve; D015415:Biomarkers / Q000097:blood*; D001706:Biopsy; D009202:Cardiomyopathies / Q000601:surgery; D005260:Female; D016027:Heart Transplantation / Q000473:pathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000601:surgery; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000097:blood / Q000235:genetics; D014184:Transplantation, Homologous / Q000473:pathology
chemical_list: D015415:Biomarkers; D012333:RNA, Messenger