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

Tuberculosis and Respiratory Diseases

article

Ju Eun Lim¹  Moo Suk Park²  Eun Young Kim²  Ji Ye Jung²  Young Ae Kang²  Young Sam Kim²  Se Kyu Kim²  Hyo Sup Shim³  Byoung Chul Cho⁴  Joon Chang² 

[1] Department of Internal Medicine, Hongik Hospital;Division of Pulmonology, Department of Internal Medicine, The Institute of Chest Disease, Yonsei University College of Medicine;Department of Pathology, Yonsei University College of Medicine;Division of Medical Oncology, Department of Internal Medicine, Yonsei University College of Medicine

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

DOI  :  10.4046/trd.2013.75.4.140

学科分类：医学（综合）

来源: The Korean Academy of Tuberculosis and Respiratory Diseases

【 摘 要 】

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). 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 .

【 授权许可】

CC BY-NC