Journal Article

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

Seemann, Stefanie, Liebenberg, Volker, Weickmann, Sabine, Wille, Ulrike, Fleischhacker, Michael, Distler, Jürgen, Tetzner, Reimo, Lewin, Jörn, Schmidt, Bernd, Schlegel, Thomas, Dietrich, Dimo, Kneip, Christoph, Field, John K, Witt, Christian, Seegebarth, Anke, Flemming, Nadja, Raji, Olaide, Walshaw, Martin, Liloglou, Triantafillos

2010

Overview

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.

• Publisher: BioMed Central,Springer Nature B.V,BMC
• Subject: Adult / Aged / Biomarkers / Biomarkers, Tumor - metabolism / Biomedical and Life Sciences / Biomedicine / Bronchi - metabolism / Bronchoscopy - methods / Cancer Research / Carcinoma - metabolism / Case-Control Studies / Clinical medicine / Colleges & universities / Confidence intervals / Disease / DNA Methylation / Epigenetics / False Positive Reactions / Female / Gene Expression Regulation, Neoplastic / Genetic testing / Health Promotion and Disease Prevention / Histology / Homeodomain Proteins - biosynthesis / Homeodomain Proteins - genetics / Hospitals / Humans / Lung cancer / Lung diseases / Lung Neoplasms - metabolism / Male / Medical research / Medicine/Public Health / Middle Aged / Nucleic Acid Hybridization / Oncology / Quality control / Research Article / Sensitivity and Specificity / Statistical analysis / Surgical Oncology / Validation studies