Vrba Lukas, Futscher Bernard W
The University of Arizona Cancer Center, The University of Arizona, Tucson, Arizona, 85724, USA.
Department of Pharmacology & Toxicology, College of Pharmacy, The University of Arizona, Tucson, Arizona, 85724, USA.
F1000Res. 2019 Dec 16;8:2106. doi: 10.12688/f1000research.21584.2. eCollection 2019.
Tumor-specific DNA methylation can be used for cancer diagnostics and monitoring. We have recently reported a set of DNA methylation biomarkers that can distinguish plasma samples from lung cancer patients versus healthy controls with high sensitivity and specificity. Furthermore, the DNA methylation signal from the biomarker loci detected in plasma samples correlated with tumor size and decreased after surgical resection of lung tumors. In order to determine the timing of DNA methylation of these loci during carcinogenesis and thus the potential of the biomarkers to detect early stages of the disease we analyzed the DNA methylation of the biomarker loci in five precancerous conditions using available data from the GEO database. We found that the DNA methylation of the biomarker loci is gained early in carcinogenesis since most of the precancerous conditions already have biomarker loci hypermethylated. Moreover, these DNA methylation biomarkers are able to distinguish between precancerous lesions with malignant potential and those that stay benign where data is available. Taken together, the biomarkers have the potential to detect the earliest cancer stages; the only limitation to detection of cancer from plasma samples or other liquid biopsies is the timing when tumors start to shed enough DNA into body fluids.
肿瘤特异性DNA甲基化可用于癌症诊断和监测。我们最近报告了一组DNA甲基化生物标志物，它们能够以高灵敏度和特异性区分肺癌患者与健康对照的血浆样本。此外，在血浆样本中检测到的生物标志物位点的DNA甲基化信号与肿瘤大小相关，并且在肺肿瘤手术切除后降低。为了确定这些位点在致癌过程中DNA甲基化的时间，从而确定生物标志物检测疾病早期阶段的潜力，我们使用来自GEO数据库的现有数据，分析了五种癌前病变中生物标志物位点的DNA甲基化情况。我们发现生物标志物位点的DNA甲基化在致癌过程早期就已出现，因为大多数癌前病变的生物标志物位点已经发生了高甲基化。此外，在有数据的情况下，这些DNA甲基化生物标志物能够区分具有恶性潜能的癌前病变和保持良性的病变。综上所述，这些生物标志物有潜力检测癌症的最早阶段；从血浆样本或其他液体活检中检测癌症的唯一限制是肿瘤开始向体液中释放足够DNA的时间。
