A poor prognosis subtype of HNSCC is consistently observed across methylome, transcriptome and miRNome analysis

摘要: Purpose: Distant metastasis after treatment is observed in about 20% of squamous cell carcinoma the head and neck (HNSCC). In absence any validated robust biomarker, patients at higher risk for cannot be provided with tailored therapy. To identify prognostic HNSCC molecular subgroups potential biomarkers, we have conducted genome-wide integrated analysis four omic sets data. Experimental Design: Using state-of-the-art technologies, a core set 45 metastasizing 55 nonmetastasizing human papillomavirus (HPV)-unrelated patient samples were analyzed different levels: gene expression (transcriptome), DNA methylation (methylome), copy number (genome), microRNA (miRNA) (miRNome). Molecular identified by model-based clustering analysis. Their clinical relevance was evaluated survival analysis, functional significance pathway enrichment Results: Patient selected transcriptome, methylome, or miRNome are associated shorter metastasis-free (MFS). A common subgroup, R1, all three approaches, statistically more significantly MFS than single omic-selected subgroups. R1 non-R1 display similar landscapes, but frequent chromosomal aberrations cluster (especially loss 13q14.2-3). tumors characterized alterations pathways involved cell–cell adhesion, extracellular matrix (ECM), epithelial-to-mesenchymal transition (EMT), immune response, apoptosis. Conclusions: Integration data across several profiles leads to better selection risk, identification relevant metastasis, discover biomarkers drug targets. Clin Cancer Res; 19(15); 4174–84. ©2013 AACR .