Pathology of the University Medical Center Schleswig-Holstein (UKSH), Campus Lübeck and the Research Center Borstel, Lübeck, Borstel, Germany.
Airway Research Center North, Member of the German Center for Lung Research (DZL), Grosshansdorf, Germany.
Clin Epigenetics. 2021 Feb 17;13(1):38. doi: 10.1186/s13148-021-01024-6.
Lung cancer is the leading cause of cancer-related death in most western countries in both, males and females, accounting for roughly 20-25% of all cancer deaths. For choosing the most appropriate therapy regimen a definite diagnosis is a prerequisite. However, histological characterization of bronchoscopic biopsies particularly with low tumor cell content is often challenging. Therefore, this study aims at (a) determining the value of DNA methylation analysis applied to specimens obtained by bronchoscopic biopsy for the diagnosis of lung cancer and (b) at comparing aberrantly CpG loci identified in bronchoscopic biopsy with those identified by analyzing surgical specimens.
We report the HumanMethylation450-based DNA methylation analysis of paired samples of bronchoscopic biopsy specimens either from the tumor side or from the contralateral tumor-free bronchus in 37 patients with definite lung cancer diagnosis and 18 patients with suspicious diagnosis. A differential DNA methylation analysis between both biopsy sites of patients with definite diagnosis identified 1303 loci. Even those samples were separated by the set of 1303 loci in which histopathological analysis could not unambiguously define the dignity. Further differential DNA methylation analyses distinguished between SCLC and NSCLC. We validated our results in an independent cohort of 40 primary lung cancers obtained by open surgical resection and their corresponding controls from the same patient as well as in publically available DNA methylation data from a TCGA cohort which could also be classified with high accuracy.
Considering that the prognosis correlates with tumor stage at time of diagnosis, early detection of lung cancer is vital and DNA methylation analysis might add valuable information to reliably characterize lung cancer even in histologically ambiguous sample material.
在大多数西方国家，肺癌无论在男性还是女性中都是导致癌症相关死亡的主要原因，占所有癌症死亡人数的 20-25%左右。为了选择最合适的治疗方案，明确的诊断是前提。然而，支气管镜活检的组织学特征，特别是肿瘤细胞含量低的情况下，往往具有挑战性。因此，本研究旨在：(a) 确定应用于支气管镜活检标本的 DNA 甲基化分析在诊断肺癌中的价值；(b) 比较支气管镜活检和手术标本分析中确定的异常 CpG 位点。
我们报告了基于 HumanMethylation450 的 DNA 甲基化分析，对 37 例明确诊断为肺癌的患者和 18 例可疑诊断的患者的支气管镜活检标本的肿瘤侧和对侧无肿瘤支气管的配对样本进行了分析。在明确诊断的患者的两个活检部位之间的差异 DNA 甲基化分析中确定了 1303 个位点。即使在组织病理学分析不能明确定义尊严的情况下，这些样本也被这组 1303 个位点分开。进一步的差异 DNA 甲基化分析区分了小细胞肺癌和非小细胞肺癌。我们在一个由开胸手术切除获得的 40 例原发性肺癌的独立队列以及来自同一患者的相应对照中验证了我们的结果，以及在 TCGA 队列中公开提供的 DNA 甲基化数据中也可以进行高准确性的分类。
考虑到预后与诊断时的肿瘤分期相关，早期发现肺癌至关重要，DNA 甲基化分析即使在组织学上有疑问的样本材料中，也可能提供有价值的信息来可靠地表征肺癌。
