Genomic and Proteomic Analysis of HPV-Associated SCCHN

描述(申请人提供)：人乳头瘤病毒(HPV)与不同类型的人类癌症的发病机制有关，包括头颈部鳞状细胞癌(SCCHN)的一个子集。这项建议涉及从HPV阳性和HPV阴性的SCCHN患者和癌前病变的新鲜组织中鉴定细胞基因表达谱。由于大多数HPV相关的SCCHN发生在口咽部(扁桃体和舌根)，我们将专门分析这一亚部位的肿瘤。需要检验的假设是，在HPV相关的SCCHN的发展过程中，基因表达谱发生了重大变化，并且这些谱是疾病的特定阶段和对治疗的反应所独有的。我们将通过使用Affymetrix GeneChips来实现我们的目标，这些基因代表了大约22,000个人类基因。我们还将检测HPV调控的E2基因以及E6和E7癌基因在SCCHN组织和癌前病变中的表达水平。病毒癌基因表达与细胞基因表达谱之间的关系将被研究。我们还计划利用SELDI-TOF质谱仪对HPV阳性和HPV阴性的SCCHN患者以及癌前病变患者进行血清蛋白质谱分析，以确定与这种疾病相关的特定生物标志物。拟议的研究代表了在分子生物学、病毒学、基因组学、蛋白质组学、免疫学、癌症生物学和生物信息学等领域拥有多学科专业知识的研究人员之间的合作努力。我们的长期目标是通过比较HPV感染的肿瘤和HPV阴性的SCCHN来更好地了解致癌HPV与肿瘤发生的关系。我们的研究将提供有关HPV阳性和HPV阴性SCCHN在肿瘤进展过程中细胞通路改变的重要信息。

DESCRIPTION (provided by applicant): Human papilloma viruses (HPVs) are involved in the pathogenesis of different types of human cancers, including a subset of squamous cell carcinoma of the head and neck (SCCHN). This proposal involves identification of cellular gene expression profiles in fresh tissues from patients with HPV-positive and HPV-negative SCCHN and premalignant lesions. Since the majority of HPV-associated SCCHN arise in the oropharynx (tonsil and base of tongue), we will specifically analyze tumors from this sub-site. The hypothesis to be tested is that significant changes in gene expression profiles occur during the development of HPV-associated SCCHN, and these profiles are unique to a particular stage of the disease and response to therapy. We will accomplish our goals by using Affymetrix GeneChips representing approximately 22,000 human genes. We will also measure the expression levels of the HPV regulatory E2 gene and the E6 and E7 oncogenes in SCCHN tissues and premalignant lesions. The relationship between viral oncogene expression and cellular gene expression profiles will be investigated. We also plan to carry out serum protein profiling in individuals with HPV-positive and HPV-negative SCCHN, and those with premalignant lesions by SELDI-TOF mass spectrometry to identify specific biomarkers associated with this disease. The proposed studies represent a collaborative effort between investigators with multidisciplinary expertise in areas such as molecular biology, virology, genomics, proteomics, immunology, cancer biology and bioinformatics. Our long-term goals are to get a better understanding of the relationship between oncogenic HPVs and carcinogenesis by comparing the HPV-infected tumors with HPV-negative SCCHN. Our studies will provide important information on cellular pathways altered during tumor progression in both HPV-positive and HPV-negative SCCHN.