title: Head and neck cancer subtypes with biological and clinical relevance: Meta-analysis of gene-expression data.
abstract: Head and neck squamous cell carcinoma (HNSCC) is a disease with heterogeneous clinical behavior and response to therapies. Despite the introduction of multimodality treatment, 40-50% of patients with advanced disease recur. Therefore, there is an urgent need to improve the classification beyond the current parameters in clinical use to better stratify patients and the therapeutic approaches. Following a meta-analysis approach we built a large training set to whom we applied a Disease-Specific Genomic Analysis (DSGA) to identify the disease component embedded into the tumor data. Eleven independent microarray datasets were used as validation sets. Six different HNSCC subtypes that summarize the aberrant alterations occurring during tumor progression were identified. Based on their main biological characteristics and de-regulated signaling pathways, the subtypes were designed as immunoreactive, inflammatory, human papilloma virus (HPV)-like, classical, hypoxia associated, and mesenchymal. Our findings highlighted a more aggressive behavior for mesenchymal and hypoxia-associated subtypes. The Genomics Drug Sensitivity Project was used to identify potential associations with drug sensitivity and significant differences were observed among the six subtypes. To conclude, we report a robust molecularly defined subtype classification in HNSCC that can improve patient selection and pave the way to the development of appropriate therapeutic strategies.
authors.affiliation: Functional Genomics and Bioinformatics, Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Loris
authors.initials: L
authors.lastname: De Cecco
authors.affiliation: Department of Mathematics, Stanford University, Stanford, CA, USA.
authors.forename: Monica
authors.initials: M
authors.lastname: Nicolau
authors.affiliation: Functional Genomics and Bioinformatics, Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Giannoccaro
authors.affiliation: Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Daidone
authors.affiliation: Head and Neck Medical Oncology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Bossi
authors.affiliation: Head and Neck Medical Oncology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Locati
authors.affiliation: Head and Neck Medical Oncology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Lisa
authors.initials: L
authors.lastname: Licitra
authors.affiliation: Functional Genomics and Bioinformatics, Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Silvana
authors.initials: S
authors.lastname: Canevari
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000145:classification* / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000821:virology; D015687:Cell Hypoxia / Q000235:genetics; D066264:Datasets as Topic; D018450:Disease Progression; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D020869:Gene Expression Profiling; D005802:Genes, MHC Class II; D018740:Genetic Heterogeneity; D006258:Head and Neck Neoplasms / Q000145:classification* / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000821:virology; D006801:Humans; D007249:Inflammation; D046228:Microarray Analysis; D009363:Neoplasm Proteins / Q000235:genetics; D027383:Papillomaviridae / Q000302:isolation & purification; D030361:Papillomavirus Infections / Q000235:genetics; D012907:Smoking / Q000235:genetics; D016896:Treatment Outcome
chemical_list: D009363:Neoplasm Proteins
keywords: HNSCC; gene expression; meta-analysis; microarray; tumor subtypes
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