TY - JOUR
T1 - Prognostic significance of urokinase plasminogen activator receptor and its cleaved forms in blood from patients with non-small cell lung cancer
AU - Almasi, Charlotte Elberling
AU - Høyer-Hansen, Gunilla
AU - Christensen, Ib Jarle
AU - Pappot, Helle
N1 - Keywords: Aged; Carcinoma, Non-Small-Cell Lung; Female; Fluoroimmunoassay; Humans; Lung Neoplasms; Male; Middle Aged; Prognosis; Receptors, Urokinase Plasminogen Activator
PY - 2009
Y1 - 2009
N2 - Urokinase plasminogen activator (uPA) cleaves its three-domain cell surface receptor, uPAR, liberating domain I [uPAR(I)] and leaving the cleaved uPAR(II-III) on the cell surface. Both intact and cleaved uPAR can be shed from the cell surface. uPAR(I) was previously shown to be a prognostic factor in lung tumour extracts. Here we analyse uPAR forms in blood from patients with non-small cell lung cancer (NSCLC). Preoperatively sampled plasma/serum from 32 patients with NSCLC was analysed. Three time-resolved fluoroimmunoassays (TR-FIAs) measuring intact uPAR(I-III) (TR-FIA 1), uPAR(I-III) + uPAR(II-III) (TR-FIA 2) and uPAR(I) (TR-FIA 3) were applied. The Spearman rank correlations between plasma and serum levels of uPAR(I-III), uPAR(I-III) + uPAR(II-III), and uPAR(I) were 0.89, 0.94 and 0.68 respectively. Survival analysis demonstrated that high levels of all uPAR forms were associated with shorter survival. Adjusted for histological subtype high plasma uPAR(I-III) and uPAR(I) levels as well as serum uPAR(I) levels were significantly associated with shorter OS (hazards ratios = 4.3, 2.8 and 3.8 respectively). High blood levels of intact uPAR and its cleaved forms are associated with poor prognosis in NSCLC.
AB - Urokinase plasminogen activator (uPA) cleaves its three-domain cell surface receptor, uPAR, liberating domain I [uPAR(I)] and leaving the cleaved uPAR(II-III) on the cell surface. Both intact and cleaved uPAR can be shed from the cell surface. uPAR(I) was previously shown to be a prognostic factor in lung tumour extracts. Here we analyse uPAR forms in blood from patients with non-small cell lung cancer (NSCLC). Preoperatively sampled plasma/serum from 32 patients with NSCLC was analysed. Three time-resolved fluoroimmunoassays (TR-FIAs) measuring intact uPAR(I-III) (TR-FIA 1), uPAR(I-III) + uPAR(II-III) (TR-FIA 2) and uPAR(I) (TR-FIA 3) were applied. The Spearman rank correlations between plasma and serum levels of uPAR(I-III), uPAR(I-III) + uPAR(II-III), and uPAR(I) were 0.89, 0.94 and 0.68 respectively. Survival analysis demonstrated that high levels of all uPAR forms were associated with shorter survival. Adjusted for histological subtype high plasma uPAR(I-III) and uPAR(I) levels as well as serum uPAR(I) levels were significantly associated with shorter OS (hazards ratios = 4.3, 2.8 and 3.8 respectively). High blood levels of intact uPAR and its cleaved forms are associated with poor prognosis in NSCLC.
U2 - 10.1111/j.1600-0463.2009.02533.x
DO - 10.1111/j.1600-0463.2009.02533.x
M3 - Journal article
C2 - 19775344
SN - 0903-465X
VL - 117
SP - 755
EP - 761
JO - APMIS. Supplementum
JF - APMIS. Supplementum
IS - 10
ER -