title: Plasminogen Activator Inhibitor Type 1 (PAI-1) A15T Gene Polymorphism Is Associated with Prognosis in Patients with EGFR Mutation Positive Pulmonary Adenocarcinoma.
abstract: BACKGROUND
  Plasminogen activator inhibitor type 1 (PAI-1), an important regulator of plasminogen activator system which controls degradation of extracellular membrane and progression of tumor cells, and PAI-1 gene polymorphic variants have been known as the prognostic biomarkers of non-small cell lung cancer patients. Recently, experimental in vitro study revealed that transforming growth factor-β1 initiated PAI-1 transcription through epithelial growth factor receptor (EGFR) signaling pathway. However, there is little clinical evidence on the association between PAI-1 A15T gene polymorphism and prognosis of Korean population with pulmonary adenocarcinoma and the influence of activating mutation of EGFR kinase domain.
  
  
  METHODS
  We retrospectively reviewed the medical records of 171 patients who were diagnosed with pulmonary adenocarcinoma and undergone EGFR mutation analysis from 1995 through 2009.
  
  
  RESULTS
  In all patients with pulmonary adenocarcinoma, there was no significant association between PAI-1 A15T polymorphic variants and prognosis for overall survival. However, further subgroup analysis showed that the group with AG/AA genotype had a shorter 3-year survival time than the group with GG genotype in patients with EGFR mutant-type pulmonary adenocarcinoma (mean survival time, 24.9 months vs. 32.5 months, respectively; p=0.015). In multivariate analysis of 3-year survival for patients with pulmonary adenocarcinoma harboring mutant-type EGFR, the AG/AA genotype carriers had poorer prognosis than the GG genotype carriers (hazard ratio, 7.729; 95% confidence interval, 1.414-42.250; p=0.018).
  
  
  CONCLUSIONS
  According to our study of Korean population with pulmonary adenocarcinoma, AG/AA genotype of PAI-1 A15T would be a significant predictor of poor short-term survival in patients with pulmonary adenocarcinoma harboring mutant-type EGFR.
authors.affiliation: Department of Internal Medicine, Hongik Hospital, Seoul, Korea.
authors.forename: Ju Eun
authors.initials: JE
authors.lastname: Lim
authors.forename: Moo Suk
authors.initials: MS
authors.lastname: Park
authors.forename: Eun Young
authors.initials: EY
authors.lastname: Kim
authors.forename: Ji Ye
authors.initials: JY
authors.lastname: Jung
authors.forename: Young Ae
authors.initials: YA
authors.lastname: Kang
authors.forename: Young Sam
authors.initials: YS
authors.lastname: Kim
authors.forename: Se Kyu
authors.initials: SK
authors.lastname: Kim
authors.forename: Hyo Sup
authors.initials: HS
authors.lastname: Shim
authors.forename: Byoung Chul
authors.initials: BC
authors.lastname: Cho
authors.forename: Joon
authors.initials: J
authors.lastname: Chang
keywords: Carcinoma, Non-Small-Cell Lung; Plasminogen Activator Inhibitor 1; Polymorphism, Single Nucleotide; Prognosis; Receptor, Epidermal Growth Factor