Over a half million new cases of Head and Neck Squamous Cell Carcinoma (HNSCC) are diagnosed annually worldwide, however, 5 year overall survival is only 50% for HNSCC patients. Recently, high throughput technologies have accelerated the genome-wide characterization of HNSCC. However, comprehensive pipelines with statistical algorithms that account for HNSCC biology and perform independent confirmatory and functional validation of candidates are needed to identify the most biologically relevant genes. We applied outlier statistics to high throughput gene expression data, and identified 76 top-scoring candidates with significant differential expression in tumors compared to normal tissues. We identified 15 epigenetically regulated candidates by focusing on a subset of the genes with a negative correlation between gene expression and promoter methylation. Differential expression and methylation of 3 selected candidates (BANK1, BIN2, and DTX1) were confirmed in an independent HNSCC cohorts from Johns Hopkins and TCGA (The Cancer Genome Atlas). We further performed functional evaluation of NOTCH regulator, DTX1, which was downregulated by promoter hypermethylation in tumors, and demonstrated that decreased expression of DTX1 in HNSCC tumors maybe associated with NOTCH pathway activation and increased migration potential.
- Klíčová slova
- DTX1, HNSCC, expression, integration, methylation,
- MeSH
- dospělí MeSH
- epigenomika * MeSH
- kohortové studie MeSH
- lidé středního věku MeSH
- lidé MeSH
- metylace DNA MeSH
- nádorové buněčné linie MeSH
- nádory hlavy a krku genetika patologie MeSH
- pohyb buněk genetika MeSH
- polymerázová řetězová reakce s reverzní transkripcí MeSH
- receptory Notch genetika MeSH
- regulace genové exprese u nádorů * MeSH
- RNA interference MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- shluková analýza MeSH
- signální transdukce genetika MeSH
- spinocelulární karcinom genetika patologie MeSH
- stanovení celkové genové exprese metody MeSH
- tumor supresorové geny * MeSH
- ubikvitinligasy genetika MeSH
- výpočetní biologie metody MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- DTX1 protein, human MeSH Prohlížeč
- receptory Notch MeSH
- ubikvitinligasy MeSH
