基于宿主基因组HPV整合位点分析寻找头颈鳞癌相关基因

Head and neck squamous cancer (HNC) is one of the most common maligant tumour. HPV infection and integration is considered to be one of the cause of HNC. However, the underlying mechanism has not been clearly clarified. Recently, a number of host-viral junction sequences have been collected in HNC tissues. Bioinformatic gene functional annotation analysis based on DAVID database was carried out to compare the potentially integration-affected host genes derived from tumour with random sites. It revealed that HPV DNA preferred to integrate into intragenic regions and gene-dense regions of human chromosomes which made it . Furthermore, analysis of the integration sites in the human genome revealed that there were several integration hotspots although all chromosomes were represented. Functional annotation analysis revealed that the integration targeted genes were enriched in tumor-related terms such as "regulation of cell cycle""regulation of cell proliferation""cell death""negative regulation of transcription factor activity" based gene ontology (GO) analysis. In line with this, 3 of 6 ITGs tested were found aberrantly expressed in head and neck cancer tissues and cell lines. .Based on the above observations, we postulate that when HPV integrated to/near human host genes which could be possessing cancer related functions, the risk of HPV integration induced cells transformation and HNC development will be great. So, based on HPV integration targeted genes, much more new HNC related genes could be found out and we will clarified the function and mechanism of these integration targeted genes..Overall, the purpose of this project was to found new HNC related genes based on comprehensive analysis of the integration targeted genes and clarify that dysregulation of integration tergeted genes caused by viral integration possibly having an etiological role involvement in head and neck carcinogenesis.

HPV感染是头颈鳞癌发生的因素之一，但其确切致癌机制尚未完全阐明。我们拟通过对HPV整合位点信息进行系统的生物信息学分析，探明HPV整合位点在宿主基因组的分布特点，通过对整合位点周围靶基因进行功能聚类（GO）分析，进一步阐明HPV是否可通过影响整合位点周围靶基因功能参与头颈鳞癌的发生，并基于此寻找新的头颈鳞癌相关基因。前期分析发现，HPV在人类染色体上的分布存在热点区域，如基因密集区域和基因外显子区域，这些为HPV整合影响宿主靶基因的表达和功能提供了前提条件。GO分析发现整合靶基因富集在细胞增殖、细胞死亡调控、细胞周期调控等与肿瘤发生发展密切相关的功能条目上。定量分析发现整合靶基因在头颈鳞癌中存在异常表达。基于此我们推测HPV可通过影响整合位点周围宿主靶基因功能从而促进肿瘤的发生发展。本研究将对整合靶基因进行深入的功能研究，检测其在头颈鳞癌中的表达情况，明确与头颈鳞癌临床病理资料的相关性。