Email updates

Keep up to date with the latest news and content from BMC Cancer and BioMed Central.

Open Access Highly Accessed Research article

SHOX2 DNA Methylation is a Biomarker for the diagnosis of lung cancer based on bronchial aspirates

Bernd Schmidt1, Volker Liebenberg2, Dimo Dietrich3*, Thomas Schlegel3, Christoph Kneip4, Anke Seegebarth5, Nadja Flemming3, Stefanie Seemann3, Jürgen Distler3, Jörn Lewin3, Reimo Tetzner3, Sabine Weickmann6, Ulrike Wille7, Triantafillos Liloglou8, Olaide Raji8, Martin Walshaw9, Michael Fleischhacker10, Christian Witt6 and John K Field8*

Author Affiliations

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

For all author emails, please log on.

BMC Cancer 2010, 10:600  doi:10.1186/1471-2407-10-600

Published: 3 November 2010

Abstract

Background

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.

Methods

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.

Results

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%]).

Conclusions

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.