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J Thorac Oncol. 2011 Oct;6(10):1632-8. doi: 10.1097/JTO.0b013e318220ef9a.

SHOX2 DNA methylation is a biomarker for the diagnosis of lung cancer in plasma.

Author information

1
Theracode GmbH, Mainz, Germany.

Abstract

INTRODUCTION:

Recently, analysis of DNA methylation of the SHOX2 locus was shown to reliably identify lung cancer in bronchial aspirates of patients with disease. As a plasma-based assay would expand the possible applications of the SHOX2 biomarker, this study aimed to develop a modified SHOX2 assay for use in a blood-based test and to analyze the performance of this optimized SHOX2 methylation assay in plasma.

METHODS:

Quantitative real-time polymerase chain reaction was used to analyze DNA methylation of SHOX2 in plasma samples from 411 individuals. A training study (20 stage IV patients with lung cancer and 20 controls) was performed to show the feasibility of detecting the SHOX2 biomarker in blood and to determine a methylation cutoff for patient classification. The resulting cutoff was verified in a testing study composed of 371 plasma samples from patients with lung cancer and controls.

RESULTS:

DNA methylation of SHOX2 could be used as a biomarker to distinguish between malignant lung disease and controls at a sensitivity of 60% (95% confidence interval: 53-67%) and a specificity of 90% (95% confidence interval: 84-94%). Cancer in patients with stages II (72%), III (55%), and IV (83%) was detected at a higher sensitivity when compared with stage I patients. Small cell lung cancer (80%) and squamous cell carcinoma (63%) were detected at the highest sensitivity when compared with adenocarcinomas.

CONCLUSIONS:

SHOX2 DNA methylation is a biomarker for detecting the presence of malignant lung disease in blood plasma from patients with lung cancer.

PMID:
21694641
DOI:
10.1097/JTO.0b013e318220ef9a
[Indexed for MEDLINE]
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