Department of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota.
Department of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota.
Cancer Epidemiol Biomarkers Prev. 2020 Dec;29(12):2642-2650. doi: 10.1158/1055-9965.EPI-20-0616. Epub 2020 Sep 18.
Discovery of methylated DNA markers (MDM) of esophageal squamous cell carcinoma (ESCC) has sparked interest in assessing these markers in tissue. We evaluated MDMs in ESCC from three geographically and ethnically distinct populations, and explored the feasibility of assaying MDMs from DNA obtained by swallowed balloon devices.
MDMs were assayed in ESCC and normal tissues obtained from the populations of United States, Iran, and China, and from exfoliative cytology specimens obtained by balloons in a Chinese population. Areas under the receiver operating curve (AUC) of MDMs discriminating ESCC from normal tissues were calculated. Random forest prediction models were built, trained on U.S. cases and controls, and calibrated to U.S.-only controls (model 1) and three-country controls (model 2). Statistical tests were used to assess the relationship between dysplasia and MDM levels in balloons.
Extracted DNA from 333 ESCC and 322 normal tissues was analyzed, in addition to archival DNA from 98 balloons. For ESCC, model 1 validated in Iranian and Chinese tissues with AUCs of 0.90 and 0.87, and model 2 yielded AUCs of 0.99, 0.96, and 0.94 in tissues from the United States, Iran, and China, respectively. In Chinese balloons, MDMs showed a statistically significant trend of increasing levels with increasing grades of dysplasia ( < 0.004).
MDMs accurately discriminate ESCC from normal esophagus in tissues obtained from high- and low-incidence countries. Preliminary data suggest that levels of MDMs assayed in DNA from swallowed balloon devices increase with dysplasia grade. Larger studies are needed to validate these results.
MDMs coupled with minimally invasive collection methods have the potential for worldwide application in ESCC screening.
发现食管鳞状细胞癌（ESCC）的甲基化 DNA 标志物（MDM）引起了人们对评估组织中这些标志物的兴趣。我们评估了来自三个地理位置和种族截然不同的人群的 ESCC 中的 MDM，并探索了从吞下气球装置获得的 DNA 中检测 MDM 的可行性。
我们在来自美国、伊朗和中国的人群中获得的 ESCC 和正常组织中以及在来自中国人群的气球获得的脱落细胞学标本中检测了 MDM。计算了区分 ESCC 与正常组织的 MDM 的接收者操作特征曲线（AUC）下的面积。构建了随机森林预测模型，在美国病例和对照中进行训练，并在仅美国对照（模型 1）和三个国家对照（模型 2）中进行校准。使用统计检验来评估在气球中发育不良与 MDM 水平之间的关系。
除了 98 个气球的存档 DNA 外，还分析了 333 个 ESCC 和 322 个正常组织的提取 DNA。对于 ESCC，模型 1 在伊朗和中国组织中得到验证，AUC 分别为 0.90 和 0.87，模型 2 在来自美国、伊朗和中国的组织中的 AUC 分别为 0.99、0.96 和 0.94。在中国气球中，MDM 随着发育不良程度的增加呈统计学上显著的水平升高趋势（<0.004）。
MDM 能够准确地区分组织中 ESCC 与正常食管。初步数据表明，从吞下的气球装置中获得的 DNA 中检测到的 MDM 水平随着发育不良程度的增加而增加。需要更大的研究来验证这些结果。
MDM 与微创采集方法相结合，有可能在全球范围内应用于 ESCC 筛查。
