Published in:
Open Access
01-12-2010 | Research article
SHOX2 DNA Methylation is a Biomarker for the diagnosis of lung cancer based on bronchial aspirates
Authors:
Bernd Schmidt, Volker Liebenberg, Dimo Dietrich, Thomas Schlegel, Christoph Kneip, Anke Seegebarth, Nadja Flemming, Stefanie Seemann, Jürgen Distler, Jörn Lewin, Reimo Tetzner, Sabine Weickmann, Ulrike Wille, Triantafillos Liloglou, Olaide Raji, Martin Walshaw, Michael Fleischhacker, Christian Witt, John K Field
Published in:
BMC Cancer
|
Issue 1/2010
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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.