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
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