Data from Early Detection of Lung Cancer Using DNA Promoter Hypermethylation in Plasma and Sputum

Abstract

<div>Abstract<p><b>Purpose:</b> CT screening can reduce death from lung cancer. We sought to improve the diagnostic accuracy of lung cancer screening using ultrasensitive methods and a lung cancer–specific gene panel to detect DNA methylation in sputum and plasma.</p><p><b>Experimental Design:</b> This is a case–control study of subjects with suspicious nodules on CT imaging. Plasma and sputum were obtained preoperatively. Cases (<i>n</i> = 150) had pathologic confirmation of node-negative (stages I and IIA) non–small cell lung cancer. Controls (<i>n</i> = 60) had non-cancer diagnoses. We detected promoter methylation using quantitative methylation-specific real-time PCR and methylation-on-beads for cancer-specific genes (<i>SOX17, TAC1, HOXA7, CDO1, HOXA9</i>, and <i>ZFP42</i>).</p><p><b>Results:</b> DNA methylation was detected in plasma and sputum more frequently in people with cancer compared with controls (<i>P</i> < 0.001) for five of six genes. The sensitivity and specificity for lung cancer diagnosis using the best individual genes was 63% to 86% and 75% to 92% in sputum, respectively, and 65% to 76% and 74% to 84% in plasma, respectively. A three-gene combination of the best individual genes has sensitivity and specificity of 98% and 71% using sputum and 93% and 62% using plasma. Area under the receiver operating curve for this panel was 0.89 [95% confidence interval (CI), 0.80–0.98] in sputum and 0.77 (95% CI, 0.68–0.86) in plasma. Independent blinded random forest prediction models combining gene methylation with clinical information correctly predicted lung cancer in 91% of subjects using sputum detection and 85% of subjects using plasma detection.</p><p><b>Conclusions:</b> High diagnostic accuracy for early-stage lung cancer can be obtained using methylated promoter detection in sputum or plasma. <i>Clin Cancer Res; 23(8); 1998–2005. ©2016 AACR</i>.</p></div>