title: The liberated domain I of urokinase plasminogen activator receptor--a new tumour marker in small cell lung cancer.
abstract: The prognosis of small cell lung cancer (SCLC) remains poor with a 5-year survival rate of 4-6%. In non-small cell lung cancer (NSCLC), high levels of intact and cleaved forms of the receptor for urokinase plasminogen activator (uPAR) are significantly associated with short overall survival. Our aim was therefore to determine the prognostic value of the different uPAR forms in blood from SCLC patients. Serum samples from 92 treatment naive SCLC patients were analysed. Intact uPAR, uPAR(I-III), intact and cleaved uPAR, uPAR(I-III) + uPAR(II-III) and the liberated domain I, uPAR(I) were measured using time-resolved fluorescence immunoassays (TR-FIA 1-3). Assessment of association of the uPAR forms to overall survival (OS) was done using Cox regression analysis adjusted for clinical covariates [age, gender, stage, lactate dehydrogenase (LDH), WHO performance status (PS)]. Multivariate survival analysis demonstrated that high levels of uPAR(I) were significantly (p = 0.009) associated with short overall survival (OS). Patients with uPAR(I) levels above the second tertile had a hazard ratio (HR) of 1.9 (95% confidence interval (CI): 1.1-3.3), compared to patients with levels below the first tertile. High serum uPAR(I) levels are associated with short OS in SCLC patient, independent of LDH and PS.
authors.affiliation: The Finsen Laboratory, Rigshospitalet/Biotech Research and Innovation Centre(BRIC), University of Copenhagen, DK-2200 Copenhagen, Denmark. ib.jarle@finsenlab.dk
authors.forename: Charlotte E
authors.initials: CE
authors.lastname: Almasi
authors.forename: Lars
authors.initials: L
authors.lastname: Drivsholm
authors.forename: Helle
authors.initials: H
authors.lastname: Pappot
authors.forename: Gunilla
authors.initials: G
authors.lastname: Høyer-Hansen
authors.forename: Ib J
authors.initials: IJ
authors.lastname: Christensen
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood; D005260:Female; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008175:Lung Neoplasms / Q000097:blood* / Q000188:drug therapy / Q000401:mortality; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011379:Prognosis; D017434:Protein Structure, Tertiary; D055293:Receptors, Urokinase Plasminogen Activator / Q000097:blood*; D012044:Regression Analysis; D055752:Small Cell Lung Carcinoma / Q000097:blood* / Q000188:drug therapy / Q000401:mortality*
chemical_list: D014408:Biomarkers, Tumor; C524898:PLAUR protein, human; D055293:Receptors, Urokinase Plasminogen Activator; D007770:L-Lactate Dehydrogenase