Portal de Periódicos da CAPES

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

2011; Elsevier BV; Volume: 6; Issue: 10 Linguagem: Inglês

10.1097/jto.0b013e318220ef9a

1556-1380

Christoph Kneip, Bernd Schmidt, Anke Seegebarth, Sabine Weickmann, Michael Fleischhacker, Volker Liebenberg, John K. Field, Dimo Dietrich,

RNA modifications and cancer

IntroductionRecently, 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.MethodsQuantitative 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.ResultsDNA 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.ConclusionsSHOX2 DNA methylation is a biomarker for detecting the presence of malignant lung disease in blood plasma from patients with lung cancer.