SHOX2 DNA methylation is a promising biomarker for the diagnosis of lung cancer in plasma
B. Schmidt, C. Kneip, A. Seegebarth, M. Fleischhacker, V. Liebenberg, D. Dietrich (Halle, Mainz, Berlin, Germany)
Source: Annual Congress 2011 - Innovative diagnostic methods for lung cancer
Session: Innovative diagnostic methods for lung cancer
Session type: Oral Presentation
Number: 4505
Disease area: Thoracic oncology
Abstract Background & Objectives: SHOX2 DNA methylation (m SHOX2) has been shown previously to identify lung cancer in bronchial aspirates and a test for m SHOX2 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 m SHOX2 in plasma and to evaluate the clinical performance in patients.Methods: A real time PCR duplex assay originally developed for quantification of m SHOX2 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 m SHOX2 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 m SHOX2 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: m SHOX2 is a promising biomarker for detection of malignant lung disease in plasma.
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B. Schmidt, C. Kneip, A. Seegebarth, M. Fleischhacker, V. Liebenberg, D. Dietrich (Halle, Mainz, Berlin, Germany). SHOX2 DNA methylation is a promising biomarker for the diagnosis of lung cancer in plasma. Eur Respir J 2011; 38: Suppl. 55, 4505
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