Plasminogen Activator Inhibitor Type 1 (PAI-1) A15T Gene Polymorphism Is Associated with Prognosis in Patients with EGFR Mutation Positive Pulmonary Adenocarcinoma.
10.4046/trd.2013.75.4.140
- Author:
Ju Eun LIM
1
;
Moo Suk PARK
;
Eun Young KIM
;
Ji Ye JUNG
;
Young Ae KANG
;
Young Sam KIM
;
Se Kyu KIM
;
Hyo Sup SHIM
;
Byoung Chul CHO
;
Joon CHANG
Author Information
1. Department of Internal Medicine, Hongik Hospital, Seoul, Korea.
- Publication Type:In Vitro ; Original Article
- Keywords:
Plasminogen Activator Inhibitor 1;
Polymorphism, Single Nucleotide;
Carcinoma, Non-Small-Cell Lung;
Prognosis;
Receptor, Epidermal Growth Factor
- MeSH:
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
- From:Tuberculosis and Respiratory Diseases
2013;75(4):140-149
- CountryRepublic of Korea
- Language:English
-
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.
