TFPI-2 methylation predicts poor prognosis in non-small cell lung cancer

Background: Methylation of human tissue factor pathway inhibitor-2 (TFPI-2) gene has been detected in several types of cancer, including non-small cell lung cancer (NSCLC). However, an association between the methylation status of TFPI-2 gene and prognosis has not yet been investigated. Methods: Methylation of TFPI-2 gene was examined in a consecutive series of 133 non-metastatic NSCLC patients using methylation-specific PCR (MSP). Univariate and multivariate analyses were conducted to investigate the association between clinical variables and overall survival time. Results: Methylation of TFPI-2 gene was detected in 36 of 133 patients (27.1%). Of these 36 patients, seventeen individuals (47.2%) carried stage III tumors. The 5-year disease free survival rate among patients carrying methylated TFPI-2 tumors was significantly lower as compared to those with unmethylated TFPI-2 tumors (35.5% versus 6.1%, P < 0.0001). Moreover, methylation of TFPI-2 gene was found to be an independent prognostic factor for poor overall survival based on multivariate analysis models (P = 0.013), as was age >62 years old (P < 0.0001) and TNM stage of disease (P < 0.0001). Conclusions: The results of the present study suggest that methylation of TFPI-2 gene is an independent factor for an unfavorable prognosis in patients with NSCLC. (C) 2011 Elsevier Ireland Ltd. All rights reserved.