SHOX2 基因启动子区甲基化作为一种液体活检标志物用于肺癌的诊断。

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

机构信息

Theracode GmbH, Mainz, Germany.

出版信息

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

DOI:10.1097/JTO.0b013e318220ef9a

PMID:21694641

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.

摘要

简介

最近，对 SHOX2 基因座的 DNA 甲基化分析显示，该分析能够可靠地识别患有疾病的患者支气管抽吸物中的肺癌。由于基于血浆的检测方法可扩展 SHOX2 生物标志物的可能应用，因此本研究旨在开发一种用于基于血液检测的改良 SHOX2 检测方法，并分析这种优化的 SHOX2 甲基化检测方法在血浆中的性能。

方法

使用定量实时聚合酶链反应分析了 411 名个体血浆样本中 SHOX2 的 DNA 甲基化。一项培训研究（20 名患有肺癌的 IV 期患者和 20 名对照者）用于证明在血液中检测 SHOX2 生物标志物的可行性，并确定用于患者分类的甲基化截止值。该截止值在由 371 名肺癌患者和对照者的血浆样本组成的测试研究中得到验证。

结果

SHOX2 的 DNA 甲基化可用作生物标志物，以区分恶性肺部疾病和对照者，其敏感性为 60%（95%置信区间：53-67%），特异性为 90%（95%置信区间：84-94%）。与 I 期患者相比，II 期（72%）、III 期（55%）和 IV 期（83%）患者的癌症检测敏感性更高。与腺癌相比，小细胞肺癌（80%）和鳞状细胞癌（63%）的检测敏感性最高。