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首页> 外文期刊>British Journal of Cancer >DNA hypermethylation analysis in sputum for the diagnosis of lung cancer: training validation set approach
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DNA hypermethylation analysis in sputum for the diagnosis of lung cancer: training validation set approach

机译：痰中DNA高甲基化分析对肺癌的诊断：训练验证集方法

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Background: Lung cancer has the highest mortality of all cancers. The aim of this study was to examine DNA hypermethylation in sputum and validate its diagnostic accuracy for lung cancer. Methods: DNA hypermethylation of RASSF1A, APC , cytoglobin, 3OST2, PRDM14, FAM19A4 and PHACTR3 was analysed in sputum samples from symptomatic lung cancer patients and controls (learning set: 73 cases, 86 controls; validation set: 159 cases, 154 controls) by quantitative methylation-specific PCR. Three statistical models were used: (i) cutoff based on Youden's J index, (ii) cutoff based on fixed specificity per marker of 96% and (iii) risk classification of post-test probabilities. Results: In the learning set, approach (i) showed that RASSF1A was best able to distinguish cases from controls (sensitivity 42.5%, specificity 96.5%). RASSF1A, 3OST2 and PRDM14 combined demonstrated a sensitivity of 82.2% with a specificity of 66.3%. Approach (ii) yielded a combination rule of RASSF1A, 3OST2 and PHACTR3 (sensitivity 67.1%, specificity 89.5%). The risk model (approach iii) distributed the cases over all risk categories. All methods displayed similar and consistent results in the validation set. Conclusions: Our findings underscore the impact of DNA methylation markers in symptomatic lung cancer diagnosis. RASSF1A is validated as diagnostic marker in lung cancer.
机译：背景：肺癌是所有癌症中死亡率最高的。这项研究的目的是检查痰中的DNA超甲基化，并验证其对肺癌的诊断准确性。方法：通过对有症状肺癌患者和对照组（学习组：73例，86例;验证组：159例，154例）的痰液样本中的RASSF1A，APC，细胞色素，3OST2，PRDM14，FAM19A4和PHACTR3的DNA超甲基化进行分析。定量甲基化特异性PCR。使用了三种统计模型：（i）基于Youden J指数的临界值，（ii）基于每个标记的固定特异性96％的临界值，以及（iii）测试后概率的风险分类。结果：在学习集中，方法（i）显示RASSF1A最能区分病例与对照（敏感性42.5％，特异性96.5％）。 RASSF1A，3OST2和PRDM14的组合显示灵敏度为82.2％，特异性为66.3％。方法（ii）产生了RASSF1A，3OST2和PHACTR3的组合规则（敏感性为67.1％，特异性为89.5％）。风险模型（方法iii）将案例分布在所有风险类别中。所有方法在验证集中显示相似且一致的结果。结论：我们的发现强调了DNA甲基化标记物在有症状肺癌诊断中的作用。 RASSF1A被确认为肺癌的诊断标志物。

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