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Prognostic significance of urokinase plasminogen activator receptor and its cleaved forms in blood from patients with non-small cell lung cancer

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Abstract:

Almasi CE, Høyer-Hansen G, Christensen IJ, Pappot H. Prognostic significance of urokinase plasminogen activator receptor and its cleaved forms in blood from patients with non-small cell lung cancer. APMIS 2009; 117: 755–61.

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.

Keywords: Non-small cell lung cancer; cleaved uPAR; prognosis; time-resolved fluoroimmunoassay; uPAR; uPAR domain I

Document Type: Research Article

DOI: http://dx.doi.org/10.1111/j.1600-0463.2009.02533.x

Publication date: October 1, 2009

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