A poor prognosis subtype of HNSCC is consistently observed across methylome, transcriptome and miRNome analysis
Menée sur 100 échantillons tumoraux prélevés sur des patients atteints d'un carcinome épidermoïde de la tête et du cou sans lien avec le papillomavirus humain, cette étude identifie un ensemble de biomarqueurs associés à la survenue de métastases
Purpose Distant metastasis after treatment is observed in about 20% of Head and Neck Squamous Cell Carcinoma (HNSCC). In the absence of any validated robust biomarker, patients at higher risk for metastasis cannot be provided with tailored therapy. In order to identify prognostic HNSCC molecular subgroups and potential biomarkers, we have performed genome-wide integrated analysis of four omic sets of data.
Experimental Design Using state-of-the art technologies, a core set of 45 metastasizing and 55 non-metastasizing HPV-unrelated HNSCC patient samples were analyzed at four different levels: gene expression (transcriptome), DNA methylation (methylome), DNA copy number (genome) and miRNA expression (miRNome). Molecular subgroups were identified by a model-based clustering analysis. Their clinical relevance was evaluated by survival analysis, and functional significance by pathway enrichment analysis.
Results Patient subgroups selected by transcriptome, methylome or miRNome integrated analysis are associated with shorter metastasis-free survival. A common subgroup, R1, selected by all three omic approaches, is statistically more significantly associated with metastasis-free survival than any of the single omic selected subgroups. R1 and non-R1 samples display similar DNA copy number landscapes, but more frequent chromosomal aberrations are observed in the R1 cluster (especially loss at 13q14.2-3). R1 tumors are characterized by alterations of pathways involved in cell-cell adhesion, ECM, EMT, immune response and apoptosis.
Conclusion Integration of data across several omic profiles leads to better selection of patients at higher risk, identification of relevant molecular pathways of metastasis, and potential to discover biomarkers and drug targets.
Clinical Cancer Research , résumé, 2013