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

• Published in: Tuberculosis and respiratory diseases Vol. 75; no. 4; pp. 140 - 149
• Main Authors: Lim, Ju Eun, Park, Moo Suk, Kim, Eun Young, Jung, Ji Ye, Kang, Young Ae, Kim, Young Sam, Kim, Se Kyu, Shim, Hyo Sup, Cho, Byoung Chul, Chang, Joon
• Format: Journal Article
• Language: Korean
• Published: 대한결핵 및 호흡기학회 30.10.2013
• Subjects: Carcinoma; Epidermal Growth Factor; Non-Small-Cell Lung; Plasminogen Activator Inhibitor 1; Polymorphism; Prognosis; Receptor; Single Nucleotide; Carcinoma; Prognosis; Receptor; Non-Small-Cell Lung; Plasminogen Activator Inhibitor 1; Single Nucleotide; Polymorphism; Epidermal Growth Factor
• ISSN: 1738-3536; 2005-6184

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.