DNA methylation profiling of non-small cell lung cancer reveals a COPD-driven immune-related signature

Thorax
Els WautersDiether Lambrechts

Abstract

Non-small cell lung cancer (NSCLC) is a heterogeneous disorder consisting of distinct molecular subtypes each characterised by specific genetic and epigenetic profiles. Here, we aimed to identify novel NSCLC subtypes based on genome-wide methylation data, assess their relationship with smoking behaviour, age, COPD, emphysema and tumour histopathology, and identify the molecular pathways underlying each subtype. Methylation profiling was performed on 49 pairs of tumour and adjacent lung tissue using Illumina 450 K arrays. Transcriptome sequencing was performed using Illumina HiSeq2000 and validated using expression data from The Cancer Genome Atlas (TCGA). Tumour immune cell infiltration was investigated by immunohistochemistry. Unsupervised hierarchical clustering of tumour methylation data revealed two subgroups characterised by a significant association between cluster membership and presence of COPD (p=0.024). Ontology analysis of genes containing differentially methylated CpGs (false discovery rate, FDR-adjusted p<0.05) revealed that immune genes were strongly enriched in COPD tumours, but not in non-COPD tumours. This COPD-specific immune signature was attributable to methylation changes in immune genes expressed either by...Continue Reading

Citations

Apr 15, 2016·Current Opinion in Pulmonary Medicine·Pablo Sanchez-Salcedo, Javier J Zulueta
Nov 15, 2016·Seminars in Cancer Biology·Diane C WangYong Zhang
Jul 25, 2018·The Journal of Immunology : Official Journal of the American Association of Immunologists·Dimitra KerdidaniMaria Tsoumakidou
Oct 21, 2016·Circulation. Cardiovascular Genetics·Roby JoehanesStephanie J London
Jan 27, 2018·Clinical Epigenetics·Mercè Mateu-JimenezEsther Barreiro
Oct 27, 2017·European Respiratory Review : an Official Journal of the European Respiratory Society·Francois Ng Kee KwongKian Fan Chung
Aug 18, 2016·Nature·Bernard ThienpontDiether Lambrechts
Sep 9, 2017·Oncotarget·Aurélie HautefortFrédéric Perros
Jul 11, 2018·Nature Medicine·Diether LambrechtsBernard Thienpont
May 14, 2019·Expert Opinion on Therapeutic Targets·Gaetano CaramoriIan M Adcock
Apr 19, 2017·Clinical Epigenetics·Isaac K SundarIrfan Rahman
Jan 17, 2017·Molecular & Cellular Oncology·Bernard ThienpontDiether Lambrechts

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