SHOX2 DNA Methylation Is a Biomarker for the Diagnosis of Lung Cancer in Plasma

• DOI: 10.1097/jto.0b013e318220ef9a
• Publication Date: 2011-06-21T06:39:45Z
• Authors: Christoph Kneip; Bernd Schmidt; Anke Seegebarth; Sabine Weickmann; Michael Fleischha...; Volker Liebenberg; John K. Field; Dimo Dietrich
• Keywords: Pulmonary and Respiratory Medicine; Male; Lung Neoplasms; Adenocarcinoma; Real-Time Polymerase Chain Reaction; Sensitivity and Specificity; Plasma; 03 medical and health sciences; 0302 clinical medicine; Short Stature Homeobox Protein; Biomarkers, Tumor; Humans; Aged; Neoplasm Staging; Homeodomain Proteins; DNA methylation; SHOX2; DNA, Neoplasm; DNA Methylation; Middle Aged; 3. Good health; Survival Rate; Treatment Outcome; Oncology; Case-Control Studies; Carcinoma, Squamous Cell; Female; Lung cancer; Follow-Up Studies

Recently, analysis of DNA methylation of the SHOX2 locus was shown to reliably identify lung cancer in bronchial aspirates of patients with disease. As a plasma-based assay would expand the possible applications of the SHOX2 biomarker, this study aimed to develop a modified SHOX2 assay for use in a blood-based test and to analyze the performance of this optimized SHOX2 methylation assay in plasma.Quantitative real-time polymerase chain reaction was used to analyze DNA methylation of SHOX2 in plasma samples from 411 individuals. A training study (20 stage IV patients with lung cancer and 20 controls) was performed to show the feasibility of detecting the SHOX2 biomarker in blood and to determine a methylation cutoff for patient classification. The resulting cutoff was verified in a testing study composed of 371 plasma samples from patients with lung cancer and controls.DNA methylation of SHOX2 could be used as a biomarker to distinguish between malignant lung disease and controls at a sensitivity of 60% (95% confidence interval: 53-67%) and a specificity of 90% (95% confidence interval: 84-94%). Cancer in patients with stages II (72%), III (55%), and IV (83%) was detected at a higher sensitivity when compared with stage I patients. Small cell lung cancer (80%) and squamous cell carcinoma (63%) were detected at the highest sensitivity when compared with adenocarcinomas.SHOX2 DNA methylation is a biomarker for detecting the presence of malignant lung disease in blood plasma from patients with lung cancer.