Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Gene expression profiling of African American vs European American HPV-negative oropharyngeal squamous cell carcinomas

ABSTRACT: Head and neck cancer (HNC) is the fifth most common malignancy worldwide with an annual mortality rate of 200,000. About 90% of HNC can be classified as head and neck squamous cell carcinomas (HNSCC), of which approximately 75% are attributed to alcohol and tobacco consumption and 25% are associated with human papillomavirus (HPV), predominantly HPV16. HPV-associated OPC have better prognosis and a more favorable response to therapy as compared to HPV-negative tumors. Differences in risk factors, age of presentation, clinical behavior and gene expression profiles indicate that HPV-positive and HPV-negative tumors develop via different molecular mechanisms and are biologically distinct. African American (AA) males have a higher incidence of HNC than any other racial/gender group, and a mortality rate almost three-fold that observed in European American (EA) males. Overall, AA patients tend to present with more HPV-negative OPC and have worse prognosis as compared to both HPV-positive and HPV-negative HNSCC in EA patients. Despite the unveiling of differential gene expression patterns, genetic and epigenetic profiles and the compilation of a mutational landscape along with preliminary TCGA data of HPV-related and unrelated HNC, the molecular determinants of the racial disparity in HNC are yet to be identified. This study aimed to compare the gene expression profiles of HPV-negative HNSCC from AA and EA patients, and determine their biological differences. ANALYSIS 2: Two-condition, on-color experiment: African American (AA) vs European American (EA) HPV-negative oropharyngeal squamous cell carcinomas. Biological replicates: 8 African American and 8 European American.

ORGANISM(S): Homo sapiens

SUBMITTER: Kim Creek

PROVIDER: E-GEOD-55543 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Head and neck cancer (HNC) is the fifth most common malignancy worldwide with an annual mortality rate of 200,000. About 90% of HNC can be classified as head and neck squamous cell carcinomas (HNSCC), of which approximately 75% are attributed to alcohol and tobacco consumption and 25 are associated with human papillomavirus (HPV), predominantly HPV16. HPV-associated OPC have better prognosis and a more favorable response to therapy as compared to HPV-negative tumors. Viral oncoproteins are capable of transforming primary human keratinocytes from either genital or oral epithelia in vitro and most likely play the same role in vivo, by disrupting cell-cycle regulatory pathways leading to a genetic progression to ano-genital cancer and OPC. However, the precise mechanisms by which HPV mediates malignant transformation of keratinocytes in the upper digestive tract epithelia are not entirely clear. HPV E7-mediated inactivation of pRb results in overexpression of p16INK4A, which is commonly used as a clinical surrogate marker for HPV positivity/activity. However, high p16INK4A alone has insufficient sensitivity and specificity as a biomarker of HPV positivity in different mucosal sub-sites of HNC. Therefore, increasing emphasis is being placed on the assessment of viral load and E7 oncogene expression, resulting in further classification of HPV positive OPC as HPV-active and HPV-inactive. Differences in risk factors, age of presentation, clinical behavior and gene expression profiles indicate that HPV-positive and HPV-negative tumors develop via different molecular mechanisms and are biologically distinct. This study aimed to compare the gene expression profiles of HPV-negative and HPV-inactive OPCs from both African American and European American patients, and determine their biological and racial differences. ANALYSIS 4: Four-condition, one-color experiment: African American (AA) HPV-inactive, African American (AA) HPV-negative, European American (EA) HPV-inactive, European American (EA) HPV-negative oropharyngeal tumor samples. Biological replicates: 4 AA HPV Inactive samples, 8 AA HPV Negative samples, 4 EA HPV Inactive samples and 8 EA HPV Negative samples,

Project description:Approximately 25% of all head and neck cancers (HNC), and up to 60% of oropharyngeal cancers (OPC) are associated with human papillomavirus (HPV), predominantly HPV16. HPV-associated OPC have better prognosis and a more favorable response to therapy as compared to HPV-negative tumors. Viral oncoproteins are capable of transforming primary human keratinocytes from either genital or oral epithelia in vitro and most likely play the same role in vivo, by disrupting cell-cycle regulatory pathways leading to a genetic progression to ano-genital cancer and OPC. However, the precise mechanisms by which HPV mediates malignant transformation of keratinocytes in the upper digestive tract epithelia are not entirely clear. HPV E7-mediated inactivation of pRb results in overexpression of p16INK4A, which is commonly used as a clinical surrogate marker for HPV positivity/activity. However, high p16INK4A alone has insufficient sensitivity and specificity as a biomarker of HPV positivity in different mucosal sub-sites of HNC. Therefore, increasing emphasis is being placed on the assessment of viral load and E7 oncogene expression, resulting in further classification of HPV positive OPC as HPV-active and HPV-inactive. Differences in risk factors, age of presentation, clinical behavior and gene expression profiles indicate that HPV-positive and HPV-negative tumors develop via different molecular mechanisms and are biologically distinct. According to some reports, the rate of HPV-associated tumors is much lower in AA patients as compared to EA patients in United States. This study aimed to compare the gene expression profiles of HPV-active, -inactive and -negative OPCs from european american patients, and determine their biological differences. ANALYSIS 3: Three-condition, one-color experiment: HPV-active, HPV-inactive and HPV-negative oropharyngeal tumor samples from european american patients. Biological replicates: 8 HPV Negative Tumors. 4 HPV Inactive Tumors. 11 HPV Active Tumors.

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Gene expression profiling of African American vs European American HPV-negative oropharyngeal squamous cell carcinomas

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