Department of Thoracic Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China.
Department of Cardiovascular Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China.
Clin Epigenetics. 2020 Mar 5;12(1):39. doi: 10.1186/s13148-020-00828-2.
We had previously developed highly sensitive DNA methylation detection to diagnose lung cancer in patients with pulmonary nodules. To validate this approach and determine clinical utility in Chinese patients with indeterminate pulmonary nodules, we assessed the diagnostic accuracy for early stage lung cancer in plasma samples.
Patients with CT-detected small lung nodules (diameter ≤ 3.0 cm) were included. Cases (n = 163) had staged IA or IB non-small cell lung cancer (NSCLC), while controls (n = 83) had non-cancerous lesions. Promoter methylation of eight lung cancer-specific genes (CDO1, TAC1, SOX17, HOXA7, HOXA9, GATA4, GATA5, and PAX5) was detected using nanoparticle-based DNA extraction (MOB) followed by qMSP.
Methylation detection for CDO1, TAC1, SOX17, and HOXA7 in plasma was significantly higher in cases compared with the benign group (p < 0.001). The sensitivity and specificity for lung cancer diagnosis using individual gene was 41-69% and 49-82%. A three-gene combination of the best individual genes has sensitivity and specificity of 90% and 71%, with area under the receiver operating curve (AUC) of 0.88, (95% CI 0.84-0.93). Furthermore, three-gene combinations detected even the smallest lung nodules, with the combination of CDO1, SOX17, and HOXA7 having the overall best performance, while the combination of CDO1, TAC1, and SOX17 was best in tumor sizes less than 1.0 cm.
Using modified MOB-qMSP, high sensitivity and specificity, for the detection of circulating tumor DNA was obtained for early stage NSCLC. This strategy has great potential to identify patients at high risk and improve the diagnosis of lung cancer at an earlier stage.
我们之前开发了一种高度敏感的 DNA 甲基化检测方法，用于诊断肺结节患者的肺癌。为了验证这种方法并确定其在中国肺结节患者中的临床应用价值，我们评估了血浆样本中早期肺癌的诊断准确性。
纳入了 CT 检测到的小肺结节（直径≤3.0cm）患者。病例组（n=163）为分期为 IA 或 IB 期的非小细胞肺癌（NSCLC）患者，而对照组（n=83）为非癌性病变患者。使用纳米颗粒 DNA 提取（MOB） followed by qMSP 检测 8 个肺癌特异性基因（CDO1、TAC1、SOX17、HOXA7、HOXA9、GATA4、GATA5 和 PAX5）的启动子甲基化。
与良性组相比，病例组血浆中 CDO1、TAC1、SOX17 和 HOXA7 的甲基化检测明显更高（p<0.001）。使用单个基因进行肺癌诊断的敏感性和特异性分别为 41-69%和 49-82%。最佳单个基因的三个基因组合的敏感性和特异性分别为 90%和 71%，受试者工作特征曲线（AUC）下面积为 0.88（95%CI 0.84-0.93）。此外，三种基因组合甚至可以检测到最小的肺结节，其中 CDO1、SOX17 和 HOXA7 的组合具有最佳的整体性能，而 CDO1、TAC1 和 SOX17 的组合在肿瘤大小小于 1.0cm 时表现最佳。
使用改良的 MOB-qMSP 检测循环肿瘤 DNA 可获得早期 NSCLC 的高灵敏度和特异性。该策略具有很大的潜力来识别高危患者，并在更早阶段提高肺癌的诊断率。
