Department of Interventional Pulmonology, University Medicine Essen, Ruhrlandklinik, University Duisburg-Essen, Tueschener Weg 40, 45239, Essen, Germany.
Center for Biostatistics, Department of Biomedical Informatics, The Ohio State University, Lincoln Tower, Department of Biomedical Informatics 1800 Cannon Drive, Columbus, OH, 43210, USA; Biobank Lab, Department of Molecular Biophysics, Faculty of Biology and Environmental Protection, University of Łódź, Łódź, Poland.
Eur J Cancer. 2021 Apr;147:142-150. doi: 10.1016/j.ejca.2021.01.032. Epub 2021 Mar 1.
BACKGROUND/INTRODUCTION: In contrast to patients who present with advanced stage lung cancer and associated poor prognosis, patients with early-stage lung cancer may be candidates for curative treatments. The results of the NELSON lung cancer screening trial are expected to stimulate the development and implementation of a lung cancer screening strategy in most countries. Widespread use of chest computed tomography scans will also result in the detection of solitary pulmonary nodules. Because reliable biomarkers to distinguish between malignant and benign lesions are lacking, tissue-based histopathological diagnostics remain the gold standard. In this study, we aimed to establish a test to assess the predictive ability of DNA hypermethylation of SHOX2 and PTGER4 in plasma to discriminate between patients with 1.) lung cancer, 2.) benign lesions, and 3.) patients with chronic obstructive pulmonary disease (COPD).
We retrospectively analysed SHOX2 and PTGER4 methylation in 121 prospectively collected plasma samples of patients with lung cancer (group 1A), benign lesions (group 1B), and COPD without nodules (group 2).
PTGER4 DNA hypermethylation was more frequently observed in patients with lung cancer than in controls (p = 0.0004). Results remained significant after correction for tumour volume, smoking status, age, and eligibility for the NELSON trial.
Detection of methylated PTGER4 in plasma DNA may serve as a biomarker to support clinical decision-making in patients with pulmonary lesions at lung cancer screening in high-risk populations. Further exploration in prospective studies is warranted.
背景/引言：与晚期肺癌和预后不良的患者相比，早期肺癌患者可能是根治性治疗的候选者。NELSON 肺癌筛查试验的结果预计将激发大多数国家制定和实施肺癌筛查策略。胸部计算机断层扫描的广泛应用也将导致孤立性肺结节的检测。由于缺乏可靠的生物标志物来区分良恶性病变，基于组织的组织病理学诊断仍然是金标准。在这项研究中，我们旨在建立一种测试，以评估 SHOX2 和 PTGER4 的 DNA 超甲基化在血浆中区分 1.）肺癌、2.）良性病变和 3.）慢性阻塞性肺疾病（COPD）患者的预测能力。
我们回顾性分析了 121 例前瞻性收集的肺癌（1A 组）、良性病变（1B 组）和无结节 COPD 患者（2 组）的 SHOX2 和 PTGER4 甲基化。
肺癌患者中 PTGER4 DNA 超甲基化的频率高于对照组（p=0.0004）。在对肿瘤体积、吸烟状况、年龄和 NELSON 试验的入选资格进行校正后，结果仍然显著。
在高风险人群的肺癌筛查中，检测血浆 DNA 中的甲基化 PTGER4 可作为支持临床决策的生物标志物，用于肺部病变患者。需要进一步在前瞻性研究中探索。
