4.6 Article

Ultrasensitive DNA hypermethylation detection using plasma for early detection of NSCLC: a study in Chinese patients with very small nodules

期刊

CLINICAL EPIGENETICS
卷 12, 期 1, 页码 -

出版社

BMC
DOI: 10.1186/s13148-020-00828-2

关键词

Lung cancer; Biomarker; DNA methylation; Plasma; Early detection

资金

  1. China National Natural Science Foundation [81000905, 81972638]
  2. Hunan Provincial Natural Science Foundation [14JJ4014]
  3. Hunan Provincial Key Area RD Program [2019SK2253]
  4. CSCO [Y-young2019-034]
  5. NIH/NCI [U01CA214165]

向作者/读者索取更多资源

PurposeWe 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.Experimental designPatients with CT-detected small lung nodules (diameter <= 3.0cm) 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.ResultsMethylation 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 1.0cm.ConclusionsUsing 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. [GRAPHICS] .

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