Epithelial-specific methylation marker: A potential plasma biomarker in advanced non-small cell lung cancer

Abstract

Background: Under physiological conditions, leukocytes contribute the majority of circulating DNA in plasma. Therefore, detection of methylation at the SHP-1 promoter 2 (SHP1P2) in plasma, which represents epithelial tumor-derived circulating nucleic acids, may serve as a potential noninvasive biomarker for non-small cell lung cancer (NSCLC). Materials and Method: A quantitative polymerase chain reaction-based assay was used to determine the level of SHP1P2 methylation in plasma. Blood samples were prospectively collected from 58 patients with advanced NSCLC, 20 patients with early NSCLC, and 52 healthy volunteers. Results: Most of the healthy volunteers exhibited undetectable levels of SHP1P2 methylation. In contrast, the pretreatment levels of SHP1P2 methylation in the patients with NSCLC were readily detectable, with a median value of 770 pg ml (0-26,500 pg ml), which was significantly higher than that of the healthy controls. Furthermore, the patients with advanced NSCLC who presented baseline levels of SHP1P2 methylation of less than 700 pg ml exhibited enhanced median progression-free survival (5.2 versus 2.6 months, p = 0.009) and improved median overall survival (12.6 versus 7.6 months, p = 0.01) compared with patients who exhibited SHP1P2 methylation levels greater than 700 pg ml. From a multivariate analysis, the levels of SHP1P2 methylation were significantly associated with survival rates in advanced NSCLC. Conclusion: Measurement of the level of SHP1P2 methylation in plasma serves as a potential noninvasive biomarker for the prognostic assessment of patients with lung cancer. This biomarker can be used to develop risk-adaptive treatments for patients with lung cancer. Copyright © 2011 by the International Association for the Study of Lung Cancer.