title: Blood levels of dual-specificity phosphatase-1 independently predict risk for post-operative morbidities causing prolonged hospitalization after coronary artery bypass grafting.
abstract: New technologies to generate high-dimensional data provide unprecedented opportunities for unbiased identification of biomarkers that can be used to optimize pre-operative planning, with the goal of avoiding costly post-operative complications and prolonged hospitalization. To identify such markers, we studied the global gene expression profiles of three organs central to the metabolic and inflammatory homeostasis isolated from coronary artery disease (CAD) patients during coronary artery bypass grafting (CABG) surgery. A total of 198 whole-genome expression profiles of liver, skeletal muscle and visceral fat from 66 CAD patients of the Stockholm Atherosclerosis Gene Expression (STAGE) cohort were analyzed. Of ~50,000 mRNAs measured in each patient, the mRNA levels of the anti-inflammatory gene, dual-specificity phosphatase-1 (DUSP1) correlated independently with post-operative stay, discriminating patients with normal (≤8 days) from those with prolonged (>8 days) hospitalization (p<0.004). To validate DUSP1 as a marker of risk for post-operative complications, we prospectively analyzed 181 patients undergoing CABG at Tartu University Hospital for DUSP1 protein levels in pre-operative blood samples. The pre-operative plasma levels of DUSP1 clearly discriminated patients with normal from those with prolonged hospitalization (p=2x10-13; odds ratio = 5.1, p<0.0001; receiver operating characteristic area under the curve = 0.80). Taken together, these results indicate that blood levels of the anti-inflammatory protein DUSP1 can be used as a biomarker for post-operative complications leading to prolonged hospitalization after CABG and therefore merit further testing in longitudinal studies of patients eligible for CABG.
authors.affiliation: The Cardiovascular Genomics Group, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Solna, Stockholm, Sweden.
authors.forename: Sara
authors.initials: S
authors.lastname: Hägg
authors.forename: Thomas
authors.initials: T
authors.lastname: Alserius
authors.forename: Peri
authors.initials: P
authors.lastname: Noori
authors.forename: Arno
authors.initials: A
authors.lastname: Ruusalepp
authors.forename: Torbjörn
authors.initials: T
authors.lastname: Ivert
authors.forename: Jesper
authors.initials: J
authors.lastname: Tegnér
authors.forename: Johan
authors.initials: J
authors.lastname: Björkegren
authors.forename: Josefin
authors.initials: J
authors.lastname: Skogsberg
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D015331:Cohort Studies; D001026:Coronary Artery Bypass / Q000009:adverse effects*; D003324:Coronary Artery Disease / Q000201:enzymology / Q000453:epidemiology / Q000601:surgery*; D054638:Dual Specificity Phosphatase 1 / Q000097:blood* / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D009017:Morbidity; D011183:Postoperative Complications / Q000201:enzymology / Q000453:epidemiology; D011446:Prospective Studies; D012307:Risk Factors; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D054638:Dual Specificity Phosphatase 1