Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands.
Department of Respiratory Medicine, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
J Clin Pathol. 2014 Aug;67(8):707-11. doi: 10.1136/jclinpath-2014-202414. Epub 2014 Jun 10.
The aim of this study is to explore DNA hypermethylation analysis in sputum and exhaled breath analysis for their complementary, non-invasive diagnostic capacity in lung cancer.
Sputum samples and exhaled breath were prospectively collected from 20 lung cancer patients and 31 COPD controls (Set 1). An additional 18 lung cancer patients and 8 controls only collected exhaled breath as validation set (Set 2). DNA hypermethylation of biomarkers RASSF1A, cytoglobin, APC, FAM19A4, PHACTR3, 3OST2 and PRDM14 was considered, and breathprints from exhaled breath samples were created using an electronic nose (eNose).
Both DNA hypermethylation markers in sputum and eNose were independently able to distinguish lung cancer patients from controls. The combination of RASSF1A and 3OST2 hypermethylation had a sensitivity of 85% with a specificity of 74%. eNose had a sensitivity of 80% with a specificity of 48%. Sensitivity for lung cancer diagnosis increased to 100%, when RASSF1A hypermethylation was combined with eNose, with specificity of 42%. Both methods showed to be complementary to each other (p≤0.011). eNose results were reproducible in Set 2.
When used in concert, RASSF1A hypermethylation in sputum and exhaled breath analysis are complementary for lung cancer diagnosis, with 100% sensitivity in this series. This finding should be further validated.
本研究旨在探索痰液和呼出气分析中的 DNA 超甲基化分析，以评估其在肺癌中的互补、非侵入性诊断能力。
前瞻性收集了 20 例肺癌患者和 31 例 COPD 对照组的痰液样本和呼出气（数据集 1）。另外还收集了 18 例肺癌患者和 8 例对照组的仅呼出气作为验证集（数据集 2）。考虑了生物标志物 RASSF1A、细胞球蛋白、APC、FAM19A4、PHACTR3、3OST2 和 PRDM14 的 DNA 超甲基化，并使用电子鼻（eNose）创建了呼出气样本的呼吸图谱。
痰液中的 DNA 甲基化标志物和 eNose 均能独立地区分肺癌患者和对照组。RASSF1A 和 3OST2 甲基化的组合具有 85%的敏感性和 74%的特异性。eNose 的敏感性为 80%，特异性为 48%。当将 RASSF1A 甲基化与 eNose 结合使用时，肺癌诊断的敏感性增加到 100%，特异性为 42%。两种方法均具有互补性（p≤0.011）。eNose 在验证集中的结果具有可重复性。
当联合使用时，痰液中的 RASSF1A 甲基化和呼出气分析互补，在本系列中具有 100%的敏感性。这一发现需要进一步验证。
