喉癌是头颈外科常见的恶性肿瘤，而发病机制尚未完全阐明。目前认为人类体表体内的微生物（microbiota）与肿瘤等疾病的关系密切，但咽喉微生物与喉癌的关系还不明确。我们前期发现喉部微环境部分菌群可能是喉癌的危险因素，发现有细菌可抑制MutS同种组织蛋白2（MutS homolog2, MSH2）基因的表达，MSH2表达下调后降低喉癌患者的生存率。MSH2是DNA错配修复系统的主要功能基因，但其参与喉癌发生的机制还不清楚。本课题拟采用MiSeq高通量测序分析喉部微环境菌群的结构，筛选出与喉癌密切相关的菌群，并分析喉癌相关菌群与MSH2功能障碍的关系。构建体外细菌干扰模型，分析喉癌相关菌群诱导MSH2功能障碍后细胞的生物学行为。此外，分析喉癌相关菌群诱导MSH2功能障碍的途径。通过上述研究，本课题力图阐明喉部microbiota结构破坏后诱导MSH2功能障碍参与喉癌发生的分子机制。

Laryngeal carcinoma is a common form of head and neck cancer, and the underlying mechanisms of which risk factors influence laryngeal carcinoma susceptibility remain elusive. The human body is colonized by a large array of microbes, known as human microbiota that play critical roles in the maintenance of the human health and disease. Aberrations of the microbiota structure may be one of important factor related to cancer and other diseases, but the possible relationship between the throat microbiota and laryngeal cancer are poorly understood currently. Our previous research found several bacterial communities might be associated with laryngeal carcinoma, and certain species may reduce the expression of MSH2 (MutS homolog2) of laryngeal carcinoma cells. Patients with lower expression level of MSH2 tended to have a higher risk of mortality compared to those of controls. MSH2 is the main member of the DNA mismatch repair system, which is essential for genome stability and recombination of chromosomes. However, it is remain uncertain the potential roles of MSH2 in the development of laryngeal cancer. The purposes of this study are to determine the composition and abundance of microbiota in the throat by high-throughput MiSeq pyrosequencing of the 16S rRNA gene, and to identify specific bacterial communities that are associated with laryngeal caner related to the disfuntion of MSH2. Validating the roles of potential microbial communities involved in the laryngeal cancer proliferation and progression, we intend to recapitulate the conditions via cell culture model. These examinations include cell cycle arrest, apoptosis rates, cell proliferation, cell migration, and cell invasion, as well as the potential signaling pathway involved in these behaviors. We also plan to explore the potential pathway by which microbiota alter the function of MSH2 in the laryngeal cancer. Taken together, this study aim to analyze the mechanisms that aberration of the throat microbiota structure interfering with MSH2 promotes laryngeal carcinoma.