Plasminogen activator inhibitor variants PAI-1 A15T and PAI-2 S413C influence lung cancer prognosis.
The plasminogen pathway plays an important role in the behavior of many tumors including lung cancer. Hence genetic variants encoding plasminogen activator (PLAU), plasminogen receptor (PLAUR), plasminogen activator inhibitor 1 (PAI-1) and plasminogen activator inhibitor 2 (PAI-2) may contribute to lung cancer prognosis. To investigate this proposition we genotyped PAI-1 A15T, PLAU L141P, PLAUR L317P and PAI-2 S413C variants in 698 patients with lung cancer, 522 with non-small cell (NSCLC) and 176 with small cell lung cancer (SCLC). PAI-1 A15T was significantly associated with overall survival (OS), with carriers of variant alleles having a worse prognosis (hazard ratio (HR)=1.14; 95% confidence interval [CI]: 1.03-1.26). An association was also detected between OS in NSCLC and carrier status for PAI-2 413C (HR=1.13; 95% CI: 1.01-1.24). These common genetic variants identified warrant further evaluation as promising prognostic markers of patient outcome.
Di Bernardo
Maria Chiara
MC
Section of Cancer Genetics, Brookes Lawley Building, Institute of Cancer Research, Sutton, Surrey SM2 5NG, United Kingdom.
Matakidou
Athena
A
Eisen
Tim
T
Houlston
Richard S
RS
D014408:Biomarkers, Tumor / Q000235:genetics*; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005838:Genotype; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D008875:Middle Aged; D009367:Neoplasm Staging; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics*; D017396:Plasminogen Activator Inhibitor 2 / Q000235:genetics; D010960:Plasminogen Activators / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D055293:Receptors, Urokinase Plasminogen Activator / Q000235:genetics; D055752:Small Cell Lung Carcinoma / Q000235:genetics* / Q000401:mortality / Q000473:pathology
D014408:Biomarkers, Tumor; C524898:PLAUR protein, human; D017395:Plasminogen Activator Inhibitor 1; D017396:Plasminogen Activator Inhibitor 2; D055293:Receptors, Urokinase Plasminogen Activator; D010960:Plasminogen Activators