SHOX2 DNA methylation is a biomarker for the diagnosis of lung cancer based on bronchial aspirates

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

Research output: Contribution to journalArticle (journal)peer-review

165 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)600
JournalBMC Cancer
Volume10
DOIs
Publication statusPublished - 3 Nov 2010

Keywords

  • Adult
  • Aged
  • Biomarkers, Tumor/metabolism
  • Bronchi/metabolism
  • Bronchoscopy/methods
  • Carcinoma/metabolism
  • Case-Control Studies
  • DNA Methylation
  • False Positive Reactions
  • Female
  • Gene Expression Regulation, Neoplastic
  • Homeodomain Proteins/biosynthesis
  • Humans
  • Lung Neoplasms/metabolism
  • Male
  • Middle Aged
  • Nucleic Acid Hybridization
  • Sensitivity and Specificity

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