呼吸道菌群通过HGF/c-Met通路调控肺癌发生及侵袭转移的作用研究

研究发现：人体呼吸道微生态的变化与肺癌的发生密切相关。申请者前期从手术样本中的16srRNA测序发现：肺癌组织中链球菌属明显增高，而远癌肺组织中以葡萄球菌属为主，进一步数据分析提示呼吸道菌群与宿主的HGF/c-Met通路及免疫应答关系密切。本课题拟聚焦“呼吸道菌群通过HGF/c-Met通路调控肺癌发生及侵袭转移的作用研究”，通过菌种感染肿瘤细胞模型和小鼠雾化暴露干预模型的建立，进一步证实呼吸道特殊菌群与肺癌HGF/c-Met信号通路的关系；在此基础上通过皮下成瘤或静脉注射转移成瘤结合局部免疫微环境分析，进一步验证菌群—通路—免疫三元互作的理论体系；最后通过特定菌群的代谢产物阻断肺癌HGF/c-Met信号通路，重塑CD8+T的免疫微环境。本项目可以为肿瘤微生物组的相关研究提供新思路，为肺癌的诊治提供新方法。

Former studies found that the dynamic changes of the respiratory microbiota are closely linked to the tumorigenesis of lung cancer. Based on our preliminary work,16srRNA sequencing data from the surgical resected lung cancer samples revealed that Streptococcus was significantly dominant in lung cancer tissues, while Staphylococcus was predominant in the proper adjacent lung tissues. Further analysis suggested that the respiratory flora was closely related to dysregulated HGF/c-Met pathway in lung cancer. The present proposal will focus on "Research on the role of respiratory flora in regulating the occurrence, invasion and metastasis of lung cancer through the HGF/c-Met pathway".Firstly we will establish bacterial infected-tumor cell models and mice aerosol exposure intervention xenograft models, and then further confirm the relationship between the respiratory specific bacteria and HGF/c-Met signaling pathway in lung cancer tumorigenesis. Secondly, by using subcutaneous neoplasia or intravenous injection metastasis models, together with in situ immune microenvironment analysis, we will further validate the theoretical assumption about flora-pathway-immunity ternary interaction. Finally, we will use the metabolic products of specific bacteria to block the HGF/c-Met signaling pathway in lung cancer cells and reshape the immune microenvironment of CD8 + T cells. This project can provide new ideas for tumor microbiome related researches and furnish new methods for the diagnosis and treatment of lung cancer.