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

ABSTRACT: PURPOSE: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. EXPERIMENTAL DESIGN: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. RESULTS: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. CONCLUSIONS: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.

SUBMITTER: Chen C

PROVIDER: S-EPMC7057485 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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

Chen Chen C Huang Xiaojie X Yin Wei W Peng Muyun M Wu Fang F Wu Xia X Tang Jingqun J Chen Mingjiu M Wang Xiang X Hulbert Alicia A Brock Malcolm V MV Liu Wenliang W Herman James G JG Yu Fenglei F

Clinical epigenetics 20200305 1

<h4>Purpose</h4>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.<h4>Experimental design</h4>Patients with CT-detected small lung nodules (diameter ≤ 3.0 cm) were included. Cases (n = 163) had staged IA or IB non-small ce ...[more]

PMID: 32138766

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Project description:AimThis study aimed to identify early clinical biomarkers from birth to 16 weeks corrected age to predict typical outcome and developmental delay in infants born very preterm or with very low birthweight.MethodA prospective cohort of infants on the Sunshine Coast, Australia, was assessed using the Premie-Neuro Examination, the General Movement Assessment (GMA), the Alberta Infant Motor Scale, and the Infant Sensory Profile 2. At 24 months corrected age, delay was identified using the Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III) and Neurosensory Motor Developmental Assessment (NSMDA).ResultsOne hundred and four infants were recruited; 79 completed outcome assessments (43 females, 36 males; mean gestational age 30 weeks [SD 1 week 6 days], mean birthweight 1346 g [SD 323]). The incidence of developmental delay (motor or cognitive) was 6.3%. Suboptimal quality of fidgety general movements (temporal organization) at 16 weeks corrected age demonstrated the best predictive accuracy (Bayley-III motor: sensitivity 100% [95% confidence interval {CI} 3-100], specificity 75% [95% CI 63-84], area under the curve [AUC] 0.87); Bayley-III cognitive: sensitivity 100% [95% CI 3-100], specificity 75% [95% CI 64-84], AUC 0.88); NSMDA motor: sensitivity 100% [95% CI 40-100], specificity 81% [95% CI 70-90], AUC 0.91 [95% CI 0.86-0.95]). GMA trajectories that combined abnormal writhing general movements at 4 to 5 weeks corrected age with suboptimal quality of fidgety movement at 16 weeks corrected age were strongly predictive of developmental delay, superior to all other clinical tools, and perinatal and demographic variables investigated (p = 0.01, Akaike information criterion method 18.79 [score corrected for small sample size], accounting for 93% of the cumulative weight).InterpretationOnly the GMA had sufficient predictive validity to act as a biomarker for both conditions: typical outcome and developmental delay (motor or cognitive). GMA trajectories that assessed both writhing general movements at 4 to 5 weeks corrected age and quality of fidgety movement at 16 weeks corrected age predicted adverse neurodevelopmental outcome, accurately differentiating between infants with typical outcomes and those at increased risk for motor or cognitive delay.

Dataset Information

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

Publications

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

Similar Datasets

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