Department of Otolaryngology-Head and Neck Cancer Research Division, Johns Hopkins School of Medicine, Baltimore, Maryland 21231, USA.
Clin Cancer Res. 2010 Jul 1;16(13):3463-72. doi: 10.1158/1078-0432.CCR-09-3304. Epub 2010 Jun 30.
Aberrant promoter hypermethylation of tumor suppressor genes is a promising marker for lung cancer detection. We investigated the likelihood of detecting aberrant DNA methylation of tumor suppressor genes in plasma samples of patients with abnormalities of the lung detected upon computed tomography (CT) scan.
In a small evaluation cohort, four gene promoters (DCC, Kif1a, NISCH, and Rarb) were found to be methylated with increased frequency in samples from cancer patients specifically. We then examined DNA from 93 plasma samples from patients with abnormal findings in the lung detected upon CT scan for aberrant methylation of these four gene promoters by quantitative fluorogenic real-time PCR. The patients were divided into two groups, ground glass opacity (n = 23) and cancerous tumors (n = 70). Plasma DNA from age-matched nodule-free individuals were used as controls (n = 80).
In plasma, 73% of patients with cancerous tumors showed methylation of at least one gene with a specificity of 71% (P = 0.0001). Only 22% patients with ground glass opacity exhibited methylation of at least one gene. When smoking history was taken into account, 72% of cancer patients with no smoking history or those who smoked <20 pack-years showed methylation of at least one gene with 100% specificity (P = 0.05) when compared with matched controls. Among heavy smokers with 20+ pack-years of smoking history, 30% of the control group and 73% of the patients with cancerous tumors showed methylation (P = 0.0001).
These biomarkers can distinguish between cancerous and noncancerous abnormal CT findings.
肿瘤抑制基因启动子异常甲基化是肺癌检测的一个有前途的标志物。我们研究了在 CT 扫描检测到肺部异常的患者的血浆样本中检测到肿瘤抑制基因异常甲基化的可能性。
在一个小的评估队列中，发现四个基因启动子（DCC、Kif1a、NISCH 和 Rarb）在癌症患者的样本中甲基化频率增加。然后，我们通过定量荧光实时 PCR 检查了 93 例来自 CT 扫描检测到肺部异常的患者的血浆样本中这四个基因启动子的异常甲基化情况。这些患者被分为两组，磨玻璃密度（n = 23）和癌性肿瘤（n = 70）。来自年龄匹配的无结节个体的血浆 DNA 用作对照（n = 80）。
在血浆中，73%的癌性肿瘤患者至少有一种基因发生甲基化，特异性为 71%（P = 0.0001）。仅有 22%的磨玻璃密度患者显示至少有一种基因发生甲基化。当考虑吸烟史时，72%的无吸烟史或吸烟<20 包年的癌症患者至少有一种基因发生甲基化，特异性为 100%（P = 0.05），与匹配的对照组相比。在有 20+包年吸烟史的重度吸烟者中，对照组的 30%和癌性肿瘤患者的 73%显示甲基化（P = 0.0001）。
这些生物标志物可以区分癌性和非癌性的 CT 异常表现。
