Methylated DNA Markers of Esophageal Squamous Cancer and Dysplasia: An International Study.
Methylated DNA Markers of Esophageal Squamous Cancer and Dysplasia: An International Study.
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食管鳞癌和发育不良的甲基化DNA标记：一项国际研究。
DOI：
10.1158/1055-9965.epi-20-0616
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发表时间：
2020-12
期刊：
影响因子：
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通讯作者：
Iyer PG
中科院分区：
文献类型：
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作者：
Qin Y;Taylor W;Bamlet WR;Ravindran A;Buglioni A;Cao X;Foote PH;Slettedahl SW;Mahoney DW;Albert PS;Kim S;Hu N;Taylor PR;Etemadi A;Sotoudeh M;Malekzadeh R;Abnet CC;Smyrk TC;Katzka D;Topazian MD;Dawsey SM;Ahlquist D;Kisiel JB;Iyer PG
发现食管 - 螺菌 - 核糖 - c菌（ESCC）的甲基化DNA标记（MDMS）引发了评估这些标记在组织中的兴趣。我们从三个地理和种族不同的人群中评估了ESCC中的MDMS，并探讨了通过通过吞咽 - 波隆式设备获得的DNA分析MDM的可行性。
MDM在美国，伊朗和中国的ESCC和正常组织中进行了测定，并根据气球在中国人群中获得的剥落性细胞学标本。计算了MDMS的接收器操作曲线（AUC）与正常区分ESCC的区域。建立了随机的森林预测模型，对美国病例和控制训练，并校准了仅美国控制措施（模型1）和三个国家控制（模型2）。使用统计测试来评估气球中发育不良和MDM水平之间的关系。
除了来自98个气球的档案DNA之外，还分析了从333个ESCC中提取的DNA，并分析了322个正常组织。对于ESCC，在伊朗和中国组织中验证的模型1分别为0.90和0.87，模型2分别在美国，伊朗和中国的组织中产生0.99、0.96和0.94。在中国气球中，MDMS随着发育不良等级的增加而显示出统计学上的显着趋势（p <0.004）。
MDM可以准确地将ESCC与高发病率国家的组织中的正常食道区分开。初步数据表明，随着发育不良等级而导致的吞咽eve eves的DNA的MDM水平会增加。需要较大的研究来验证这些结果。
MDM和最小侵入性收集方法具有在ESCC筛选中应用全球应用的潜力。
Discovery of methylated-DNA-markers (MDMs) 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 from the US, Iran, and China, and from exfoliative cytology specimens obtained by balloons in a Chinese population. Areas under the receiver- operating-curve (AUCs) of MDMs discriminating ESCC from normal were calculated. Random forest prediction models were built, trained on US cases and controls and calibrated to US-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 were 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 US, Iran, and China, respectively. In Chinese balloons, MDMs showed a statistically significant trend of increasing levels with increasing grades of dysplasia (p<0.004). MDMs accurately discriminate ESCC from normal esophagus in tissues 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 world-wide application in ESCC screening.