Genomic and Proteomic Analysis of HPV-Associated SCCHN

描述（由申请人提供）：人乳头瘤病毒（hpv）参与不同类型人类癌症的发病机制，包括头颈部鳞状细胞癌（SCCHN）的一个亚群。该建议涉及鉴定hpv阳性和hpv阴性SCCHN和癌前病变患者新鲜组织中的细胞基因表达谱。由于大多数hpv相关的SCCHN发生在口咽部（扁桃体和舌根），我们将专门分析这个亚部位的肿瘤。待验证的假设是，在hpv相关SCCHN的发展过程中，基因表达谱发生了显著变化，这些谱对于疾病的特定阶段和对治疗的反应是独特的。我们将通过使用代表大约22,000个人类基因的Affymetrix基因芯片来实现我们的目标。我们还将测量HPV调控E2基因和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。我们还计划通过SELDI-TOF质谱法对hpv阳性和hpv阴性SCCHN患者以及癌前病变患者进行血清蛋白分析，以确定与该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具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，更好地了解致癌hpv与癌变之间的关系。我们的研究将为hpv阳性和hpv阴性SCCHN在肿瘤进展过程中改变的细胞通路提供重要信息。

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.