Abstract
BackgroundLung 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.ResultsWe 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.ConclusionsConsidering 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.
Highlights
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
In order to address these particularities inherent to bronchoscopic biopsies as compared to primary lung cancers, this study focuses on characterizing altered DNA methylation patterns in tumor-containing as compared to matched normal specimens collected during bronchoscopy available to pathologists for performing diagnosis
To identify recurrent epigenetic alterations in lung cancer and to reveal their putative benefit for diagnostics, HumanMethylation450 BeadChip analyses were performed on biopsy samples collected during bronchoscopy, lung cancer specimens of surgically resected primary tumors and corresponding normal lung control specimens collected from the same patients (Additional file 2: Fig. S1)
Summary
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. Some authors speculated about the putative application of these data to develop tools such as DNA methylation-based panels for diagnostic purposes [5]. Most of these analyses have been performed using surgically resected lung cancer specimens of high quality and/or high tumor cell content. The histology of biopsy specimens e.g. collected during bronchoscopy, is often more difficult to assess as compared to primary tumor specimens This is reflected e.g. in a lower overall amount of available tissue and/or a lower tumor cell content, which both can render detection and characterization of tumor cells sometimes challenging. The sample material used for building a classifier should be considered thoroughly in advance
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
