title: Plasminogen activator inhibitor variants PAI-1 A15T and PAI-2 S413C influence lung cancer prognosis.
abstract: 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.
authors.affiliation: Section of Cancer Genetics, Brookes Lawley Building, Institute of Cancer Research, Sutton, Surrey SM2 5NG, United Kingdom.
authors.forename: Maria Chiara
authors.initials: MC
authors.lastname: Di Bernardo
authors.forename: Athena
authors.initials: A
authors.lastname: Matakidou
authors.forename: Tim
authors.initials: T
authors.lastname: Eisen
authors.forename: Richard S
authors.initials: RS
authors.lastname: Houlston
mesh_terms: 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
chemical_list: 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