SHOX2 DNA Methylation is a Biomarker for the diagnosis of lung cancer based on bronchial aspirates
1 Universitätsklinik und Poliklinik für Innere Medizin I, Universitätsklinikum Halle (Saale), Halle, Germany
2 Metanomics Health GmbH, Berlin, Germany
3 Epigenomics AG, Berlin, Germany
4 Theracode GmbH, Mainz, Germany
5 Bavarian Nordic GmbH, Berlin, Germany
6 Medizinische Klinik m.S. Infektiologie und Pneumologie, Charité-Universitätsmedizin, Berlin, Germany
7 Berlin Institute of Technology, Institute for Biotechnology, Berlin, Germany
8 Roy Castle Lung Cancer Research Programme, University of Liverpool Cancer Research Centre, Liverpool L3 9TA, UK
9 Liverpool Heart & Chest Hospital NHS Trust, Thomas Drive, Liverpool L14 3PE, UK
10 Medizinische Klinik m.S. Hämatologie Onkologie, Charité-Universitätsmedizin, Berlin, Germany
BMC Cancer 2010, 10:600 doi:10.1186/1471-2407-10-600Published: 3 November 2010
This study aimed to show that SHOX2 DNA methylation is a tumor marker in patients with suspected lung cancer by using bronchial fluid aspirated during bronchoscopy. Such a biomarker would be clinically valuable, especially when, following the first bronchoscopy, a final diagnosis cannot be established by histology or cytology. A test with a low false positive rate can reduce the need for further invasive and costly procedures and ensure early treatment.
Marker discovery was carried out by differential methylation hybridization (DMH) and real-time PCR. The real-time PCR based HeavyMethyl technology was used for quantitative analysis of DNA methylation of SHOX2 using bronchial aspirates from two clinical centres in a case-control study. Fresh-frozen and Saccomanno-fixed samples were used to show the tumor marker performance in different sample types of clinical relevance.
Valid measurements were obtained from a total of 523 patient samples (242 controls, 281 cases). DNA methylation of SHOX2 allowed to distinguish between malignant and benign lung disease, i.e. abscesses, infections, obstructive lung diseases, sarcoidosis, scleroderma, stenoses, at high specificity (68% sensitivity [95% CI 62-73%], 95% specificity [95% CI 91-97%]).
Hypermethylation of SHOX2 in bronchial aspirates appears to be a clinically useful tumor marker for identifying subjects with lung carcinoma, especially if histological and cytological findings after bronchoscopy are ambiguous.