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Determine differences in gene expression between OPSCC cell lines with different sensitivity to IR

ABSTRACT: mRNA sequencing was performed on 10 oropharyngeal cancer cell lines (5 HPV-positive and 5 HPV-negative cell lines) for this project. Two cell lines (CU-OP-17 and CU-OP-20) were newly derived from HPV-negative and HPV-positive tonsil cancers, respectively (described in " Sensitivity of human papillomavirus-positive and -negative oropharyngeal cancer cell lines to ionizing irradiation" by Holzhauser et al. This study was performed with the goal to identify differences in gene expression between irradiated and non-irradiated cell line samples. Additionally, the aim was to identify possible changes in genes, involved in DNA repair or DNA damage response of the HPV-positive and HPV-negative cell lines. The data published showed an increase of HPV integration sites after irradiation. Additionally, all HPV-positive cell lines in this study showed expression of HPV encoded genes. However, no direct correlation of changes or expression of DNA repair genes was identified.

ORGANISM(S): Homo sapiens

PROVIDER: GSE153966 | GEO | 2020/07/08

REPOSITORIES: GEO

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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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Determine differences in gene expression between OPSCC cell lines with different sensitivity to IR

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