RT Journal Article SR Electronic T1 SHOX2 DNA methylation is a promising biomarker for the diagnosis of lung cancer in plasma JF European Respiratory Journal JO Eur Respir J FD European Respiratory Society SP 4505 VO 38 IS Suppl 55 A1 Bernd Schmidt A1 Christoph Kneip A1 Anke Seegebarth A1 Michael Fleischhacker A1 Volker Liebenberg A1 Dimo Dietrich YR 2011 UL http://erj.ersjournals.com/content/38/Suppl_55/4505.abstract AB Background & objectives: SHOX2 DNA methylation (mSHOX2) has been shown previously to identify lung cancer in bronchial aspirates and a test for mSHOX2 is available in Europe as an IVD test to aid pathologists in the diagnosis of lung cancer. DNA methylation biomarkers can also be used to detect tumor-derived circulating DNA in blood. The objective of the present study was to develop a modified assay for detection of mSHOX2 in plasma and to evaluate the clinical performance in patients.Methods: A real time PCR duplex assay originally developed for quantification of mSHOX2 in a high background of unmethylated DNA in bronchial aspirates was modified for the unique requirements of plasma. Following assay optimization, quantitative real-time PCR was used to analyze mSHOX2 in plasma samples (n = 411). A training study was performed to determine a cut-off for patient classification (n = 20 lung cancer patients, n = 20 controls) and the resulting cut-off was verified in a testing study (n = 202 stages I – IV lung cancer patients, n = 169 controls, including patients with other cancers like e.g. of prostate).Results: The assay reliably detected 15 pg of methylated DNA in a background of 50,000 pg unmethylated DNA. The mSHOX2 assay differentiated lung cancer patients from controls with a sensitivity of 60% and a specificity of 90%. Patients with stages II (72%), III (55%) and IV (83%) lung cancer were detected at a higher sensitivity as compared with stage I patients (27%). Small-cell lung cancer (80%) and squamous cell carcinoma (63%) were detected at higher sensitivity than adenocarcinoma (39%).Conclusions: mSHOX2 is a promising biomarker for detection of malignant lung disease in plasma.