Inter-Department Program of Biomedical Sciences, Faculty of Graduate School, Chulalongkorn University, Bangkok, Thailand.
J Thorac Oncol. 2011 Nov;6(11):1818-25. doi: 10.1097/JTO.0b013e318226b46f.
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).
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.
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(-1) (0-26,500 pg ml(-1)), 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(-1) 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(-1). From a multivariate analysis, the levels of SHP1P2 methylation were significantly associated with survival rates in advanced NSCLC.
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.
在生理条件下，白细胞是血浆中循环 DNA 的主要来源。因此，检测血浆中 SHP-1 启动子 2（SHP1P2）的甲基化，代表上皮肿瘤衍生的循环核酸，可能成为非小细胞肺癌（NSCLC）的一种潜在非侵入性生物标志物。
采用定量聚合酶链反应检测法测定血浆中 SHP1P2 甲基化水平。前瞻性收集 58 例晚期 NSCLC 患者、20 例早期 NSCLC 患者和 52 名健康志愿者的血液样本。
大多数健康志愿者的 SHP1P2 甲基化水平无法检测到。相比之下，NSCLC 患者的 SHP1P2 甲基化预处理水平很容易检测到，中位数为 770pg/ml（0-26500pg/ml），明显高于健康对照组。此外，基线 SHP1P2 甲基化水平低于 700pg/ml 的晚期 NSCLC 患者中位无进展生存期（5.2 个月与 2.6 个月，p=0.009）和中位总生存期（12.6 个月与 7.6 个月，p=0.01）均有所提高。多变量分析显示，SHP1P2 甲基化水平与晚期 NSCLC 患者的生存率显著相关。
血浆中 SHP1P2 甲基化水平的测量可作为肺癌患者预后评估的潜在非侵入性生物标志物。该生物标志物可用于为肺癌患者制定风险适应治疗。
