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Genome-wide LOH and DNA copy number alteration in HPV-neg OSCC and their associations with disease-specific survival

ABSTRACT: Oral squamous cell carcinoma (OSCC) is associated with high case-fatality. To gain insight into the complexity of OSCC and to identify potential chromosomal changes that may be associated with OSCC mortality, we examined paired DNA from peripheral blood and tumor cells to assess genome-wide LOH and DNA copy number alteration (CNA) and their associations with risk factors, tumor characteristics, and disease-specific mortality among 75 patients with HPV-negative OSCC. We found a highly heterogeneous and complex genomic landscape of HPV-negative tumors, and identified regions in 4q, 8p, 9p, and 11q that seem to play an important role in oral cancer biology and survival from this disease.

ORGANISM(S): Homo sapiens

PROVIDER: GSE68717 | GEO | 2016/03/23

SECONDARY ACCESSION(S): PRJNA283500

REPOSITORIES: GEO

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Genome-wide LOH and DNA copy number alteration in HPV-neg OSCC and their associations with disease-specific survival

Project description:Oral squamous cell carcinoma (OSCC) is associated with high case-fatality. To gain insight into the complexity of OSCC and to identify potential chromosomal changes that may be associated with OSCC mortality, we examined paired DNA from peripheral blood and tumor cells to assess genome-wide LOH and DNA copy number alteration (CNA) and their associations with risk factors, tumor characteristics, and disease-specific mortality among 75 patients with HPV-negative OSCC. We found a highly heterogeneous and complex genomic landscape of HPV-negative tumors, and identified regions in 4q, 8p, 9p, and 11q that seem to play an important role in oral cancer biology and survival from this disease. We used Affymetrix 6.0 SNP arrays to test paired DNA from peripheral blood and tumor cells isolated by laser capture microdissection from 75 patients with HPV-negative OSCC. Peripheral blood DNA is used as reference for CNA to LOH.

2016-03-23 | E-GEOD-68717 | biostudies-arrayexpress

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Project description:Human Papillomavirus (HPV) infection has been recently linked to a subset of cancers affecting the oral cavity. However, the molecular mechanisms underlying HPV-driven oral squamous cell carcinoma (OSCC) onset and/ progression are poorly understood. Methods: We perform a MS-based proteomic profiling based on HPV status on OSCC in young patients, following biological characterization and cell assays to explore the proteome functional landscape. Results: Thirty-nine proteins are differentially abundant between HPV (+) and HPV (-) OSCC. Among them, COPS3, DYHC1, and S100A8 are unfavorable for tumor recurrence and survival in contrast to A2M and Serpine1, which low levels show association with better DFS. Remarkably, S100A8 is considered an independent prognostic factor for lower survival rate, and at high levels, it alters tumor-associated immune profiling, showing a lower proportion of M1 macrophages and dendritic cells. HPV (+) OSCC also displayed the pathogen-associated patterns receptor which, when activated, triggered S100A8 and NFκB inflammatory responses. Conclusion: HPV (+) OSCC has a peculiar microenvironment pattern, distinctively of HPV (-), involving expression of pathogen-associated pattern receptors, S100A8 overexpression, and NFκB activation and responses that had important consequences in prognosis and may guide therapeutic decisions.

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