The complex between urokinase (uPA) and its type-1 inhibitor (PAI-1) in pulmonary adenocarcinoma: relation to prognosis.
In a lung cancer population comprising tumor tissue from 99 pulmonary adenocarcinoma patients, the relationship between tumor tissue level of the complex formed of urokinase (uPA) and its type-1 inhibitor (PAI-1) and survival was studied. The study included patient material previously investigated for the prognostic impact of PAI-1 on survival. Standard clinical parameters were available and the patients had a median survival time of 25 months. An ELISA established to measure preformed uPA-PAI-1 complexes was applied to the tumor extracts and previously measured data on uPA and PAI-1 levels were available. The amounts of uPA-PAI-1 complex measured in pulmonary adenocarcinoma tissue were within the same range as previously reported in breast cancer tissue (0.11-5.74 ng/mg protein). uPA and PAI-1 levels were weakly correlated to the uPA-PAI-1 complex, r = 0.52 and r = 0.47, respectively, and no relation was found between uPA-PAI-1 complex and any of the clinical parameters. However, a significant prognostic impact of PAI-1 on prognosis was demonstrated (HR = 1.62, p = 0.04). Patients with high PAI-1 and low uPA-PAI-1 complex were found to have a significantly poorer survival than patients with low PAI-1 and high uPA-PAI-1 complex (HR = 3.06, p = 0.01). This is the first investigation of the prognostic impact of uPA-PAI-1 complex in a tumor type other than breast cancer, showing low levels of uPA-PAI-1 complex in combination with high levels of PAI-1 to be associated with poor prognosis. To understand these interactions and the clinical importance of the tissue levels of uPA, PAI-1 and uPA-PAI-1 complex, the results suggest further exploratory studies of the components in pulmonary adenocarcinomas and other cancers.
Pappot
Helle
H
The Finsen Laboratory, Rigshospitalet, Copenhagen, Denmark. pappot@rh.dk
Pedersen
Anders N
AN
Brünner
Nils
N
Christensen
Ib J
IJ
D000230:Adenocarcinoma / Q000378:metabolism* / Q000401:mortality; D000328:Adult; D000368:Aged; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism*; D011379:Prognosis; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism*
D017395:Plasminogen Activator Inhibitor 1; D014568:Urokinase-Type Plasminogen Activator