Abstract 3820: Ultrasensitive DNA methylation detection using sputum and plasma for early detection of NSCLC

Abstract

Abstract Purpose: The National Lung Cancer Screening Trial provides hope that early detection can result in a reduction of mortality from lung cancer. This study was to determine if molecular alterations of sputum and plasma in patients with CT detected pulmonary nodules could predict patients with malignancy from those without. Materials and Methods: We conducted a prospective case-control study obtaining cases and controls from the Lung Cancer Spore Trial at Johns Hopkins Hospital. Plasma, sputum and pre-operative CT scans were obtained from all patients. We processed the plasma, sputum and tumor by using promoter Methylation on beads followed by quantitative methylation specific real-time PCR to investigate promoter methylation status of six cancer-related genes, CDO1, TAC1, HOXA7, HOXA9, SOX17 and ZFP42. Results: 223 patients were analyzed, including 162 patients with NSCLC and 61 patients with benign lesions. The sensitivity and specificity values for lung cancer detection in plasma, sputum or in both are shown. Plasma methylation seems to be more specific than sputum methylation. Both concomitant methylation in both plasma and sputum yielded the highest specificity for all gene combinations. Promoter methylation of CDO1, TAC1, HOXA9 and SOX17 has a high specificity but low sensitivity to detect lung cancer. Sensitivity and specificity for lung cancer detection using methylation changes in plasma and sputumPlasmaPlasmaSputumSputumPlasma & SputumPlasma & SputumGeneSpecificitySensitivitySpecificitySensitivitySpecificitySensitivityCDO180%45%67%63%93%26%TAC167%52%40%65%80%31%HOXA7100%11%80%27%100%6%HOXA960%66%7%90%67%60%SOX1767%56%73%52%93%27%ZFP4247%69%33%74%60%52%4 or more genes67%50%67%63%97%26%CDO1, TAC1, HOXA9, SOX1787%39%80%40%93%15% Conclusion: Our gene panel of promoter methylation has a high enough specificity to be clinical useful but its sensitivity is low. The integration of this panel with other biomarkers would be needed to create a platform of high enough specificity and sensitivity to be clinically applicable. Citation Format: Chen Chen, Alicia Hulbert, Alejandro Stark, Kristen Rodgers, Beverly Lee, Malcolm Brock, James Herman. Ultrasensitive DNA methylation detection using sputum and plasma for early detection of NSCLC. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3820. doi:10.1158/1538-7445.AM2015-3820