Diagnosis of pulmonary nodules by DNA methylation analysis in bronchoalveolar lavage fluids.

Diagnosis of pulmonary nodules by DNA methylation analysis in bronchoalveolar lavage fluids.
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支气管肺泡灌洗液DNA甲基化分析诊断肺结节

DOI:
10.1186/s13148-021-01163-w
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发表时间:
2021-10-07
影响因子:
5.7
通讯作者:
Liu D
Liu D
中科院分区:
医学1区
文献类型:
--
作者:
Li L;Ye Z;Yang S;Yang H;Jin J;Zhu Y;Tao J;Chen S;Xu J;Liu Y;Liang W;Wang B;Yang M;Huang Q;Chen Z;Li W;Fan JB;Liu D

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肺癌是癌症相关死亡的首要原因。DNA甲基化的改变在肺癌的发展中起主要作用。甲基化生物标志物成为肺癌诊断的一种可能方法。 我们确定了11种肺癌特异性甲基化标志物(CDO1、GSHR、HOXA11、HOXB4 - 1、HOXB4 - 2、HOXB4 - 3、HOXB4 - 4、LHX9、MIR196A1、PTGER4 - 1和PTGER4 - 2),它们能够区分肺部良恶性结节。这些标志物在恶性组织中的甲基化水平显著更高。在支气管肺泡灌洗液(BALF)样本中,甲基化信号与组织中保持相同的差异趋势。从这11种标志物的所有可能组合中开发出了一种用于肺部结节诊断(恶性与良性)的最佳5标志物模型。在测试集(57个组织样本和71个BALF样本)中,曲线下面积(AUC)值达到0.93,在特异性为91%时,总体灵敏度为82%。在一个独立验证集(111个BALF样本)中,AUC为0.82,特异性为82%,灵敏度为70%。 该模型能够将肺腺癌和鳞状细胞癌与良性疾病区分开来,特别是对于感染、炎症和结核病。该模型的性能不受性别、年龄、吸烟史或结节实性成分的影响。 网络版包含补充材料,可在10.1186/s13148 - 2021 - 01163 - w获取。
Lung cancer is the leading cause of cancer-related mortality. The alteration of DNA methylation plays a major role in the development of lung cancer. Methylation biomarkers become a possible method for lung cancer diagnosis. We identified eleven lung cancer-specific methylation markers (CDO1, GSHR, HOXA11, HOXB4-1, HOXB4-2, HOXB4-3, HOXB4-4, LHX9, MIR196A1, PTGER4-1, and PTGER4-2), which could differentiate benign and malignant pulmonary nodules. The methylation levels of these markers are significantly higher in malignant tissues. In bronchoalveolar lavage fluid (BALF) samples, the methylation signals maintain the same differential trend as in tissues. An optimal 5-marker model for pulmonary nodule diagnosis (malignant vs. benign) was developed from all possible combinations of the eleven markers. In the test set (57 tissue and 71 BALF samples), the area under curve (AUC) value achieves 0.93, and the overall sensitivity is 82% at the specificity of 91%. In an independent validation set (111 BALF samples), the AUC is 0.82 with a specificity of 82% and a sensitivity of 70%. This model can differentiate pulmonary adenocarcinoma and squamous carcinoma from benign diseases, especially for infection, inflammation, and tuberculosis. The model’s performance is not affected by gender, age, smoking history, or the solid components of nodules. The online version contains supplementary material available at 10.1186/s13148-021-01163-w.
DOI: 10.18632/oncotarget.10007
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