title: Discovery of the gene signature for acute lung injury in patients with sepsis.
abstract: The acute respiratory distress syndrome (ARDS)/acute lung injury (ALI) was described 30 yr ago, yet making a definitive diagnosis remains difficult. The identification of biomarkers obtained from peripheral blood could provide additional noninvasive means for diagnosis. To identify gene expression profiles that may be used to classify patients with ALI, 13 patients with ALI + sepsis and 20 patients with sepsis alone were recruited from the Medical Intensive Care Unit of the University of Pittsburgh Medical Center, and microarrays were performed on peripheral blood samples. Several classification algorithms were used to develop a gene signature for ALI from gene expression profiles. This signature was validated in an independently obtained set of patients with ALI + sepsis (n = 8) and sepsis alone (n = 1). An eight-gene expression profile was found to be associated with ALI. Internal validation found that the gene signature was able to distinguish patients with ALI + sepsis from patients with sepsis alone with 100% accuracy, corresponding to a sensitivity of 100%, a specificity of 100%, a positive predictive value of 100%, and a negative predictive value of 100%. In the independently obtained external validation set, the gene signature was able to distinguish patients with ALI + sepsis from patients with sepsis alone with 88.9% accuracy. The use of classification models to develop a gene signature from gene expression profiles provides a novel and accurate approach for classifying patients with ALI.
authors.affiliation: Division of Pulmonary, Allergy and Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA. howrylakj@upmc.edu
authors.forename: Judie A
authors.initials: JA
authors.lastname: Howrylak
authors.forename: Tamas
authors.initials: T
authors.lastname: Dolinay
authors.forename: Lorrie
authors.initials: L
authors.lastname: Lucht
authors.forename: Zhaoxi
authors.initials: Z
authors.lastname: Wang
authors.forename: David C
authors.initials: DC
authors.lastname: Christiani
authors.forename: Jigme M
authors.initials: JM
authors.lastname: Sethi
authors.forename: Eric P
authors.initials: EP
authors.lastname: Xing
authors.forename: Michael P
authors.initials: MP
authors.lastname: Donahoe
authors.forename: Augustine M K
authors.initials: AM
authors.lastname: Choi
mesh_terms: D018806:APACHE; D055371:Acute Lung Injury / Q000150:complications / Q000175:diagnosis / Q000235:genetics*; D000465:Algorithms; D016000:Cluster Analysis; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018805:Sepsis / Q000150:complications / Q000175:diagnosis / Q000235:genetics*