Tuberc Respir Dis.  2013 Oct;75(4):140-149.

Plasminogen Activator Inhibitor Type 1 (PAI-1) A15T Gene Polymorphism Is Associated with Prognosis in Patients with EGFR Mutation Positive Pulmonary Adenocarcinoma

Affiliations
  • 1Department of Internal Medicine, Hongik Hospital, Seoul, Korea.
  • 2Division of Pulmonology, Department of Internal Medicine, The Institute of Chest Disease, Yonsei University College of Medicine, Seoul, Korea. CHANG@yuhs.ac
  • 3Department of Pathology, Yonsei University College of Medicine, Seoul, Korea.
  • 4Division of Medical Oncology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.

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-beta1 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).
CONCLUSION
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.

Keyword

Plasminogen Activator Inhibitor 1; Polymorphism, Single Nucleotide; Carcinoma, Non-Small-Cell Lung; Prognosis; Receptor, Epidermal Growth Factor

MeSH Terms

Adenocarcinoma*
Biomarkers
Carcinoma, Non-Small-Cell Lung
Genotype
Humans
Medical Records
Membranes
Multivariate Analysis
Phosphotransferases
Plasminogen Activator Inhibitor 1
Plasminogen Activators*
Plasminogen*
Polymorphism, Single Nucleotide
Prognosis*
Receptor, Epidermal Growth Factor
Retrospective Studies
Phosphotransferases
Plasminogen
Plasminogen Activator Inhibitor 1
Plasminogen Activators
Receptor, Epidermal Growth Factor

Figure

  • Figure 1 (A) Kaplan-Meier curves for the relationship between plasminogen activator inhibitor type 1 (PAI-1) A15T genotype and 3-year survival in patients with pulmonary adenocarcinoma harboring mutant-type. Subgroup analysis of 3-year survival for the patients with pulmonary adenocarcinoma harboring wild-type epithelial growth factor receptor (EGFR) and mutant-type EGFR revealed that group with AG/AA genotype and mutant-type EGFR had a shorter survival time than group with GG genotype and mutant-type EGFR (mean survival time, 24.9 months vs. 32.5 months, respectively; p=0.015). (B) Kaplan-Meier curves for the relationship between PAI-1 A15T genotype and 3-year survival in patients with pulmonary adenocarcinoma harboring wild-type EGFR. No correlation existed between the genotypes and 3-year survival among patients with pulmonary adenocarcinoma harboring wild-type EGFR (log-rank test, p=0.589).


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