基于多组学技术的上消化道菌群与食管癌及其癌前病变关联的多中心前瞻性队列研究

食管癌高危人群精准识别是食管癌筛查及早诊早治中亟待解决的关键问题。研究证实上消化道菌群多样性在正常人、癌前病变和食管癌患者中存在差异，识别菌群的特征性变化具有初筛、浓缩食管癌高危人群的潜在应用前景。项目组前期研究发现梭菌属丰度在食管癌和癌旁组织中呈现差异性分布，口腔菌群多样性随食管癌前病变进展逐渐降低，但这些发现尚缺乏特异性活性菌株水平证据及前瞻性研究证实。本研究基于多中心食管癌高发现场前瞻性队列，首先采用人群为基础的病例对照设计，联合应用宏基因组学和培养组学技术，筛选与食管癌及其癌前病变相关的特异性活性菌株，采用动物实验进行功能验证；其次开展队列人群二次随访，采用logistic回归和随机森林方法，结合宏观环境暴露因素，构建基于上消化道特异性活性菌株的食管癌及其癌前病变预测模型，为食管癌高危人群精准识别及筛查技术方案优化提供循证医学依据。

Precise identification of high-risk population of esophageal cancer is a key problem to be solved in esophageal cancer screening as well as early diagnosis and treatment. Previous studies have confirmed that the diversity of upper gastrointestinal microbiome is different among normal people, patients with precancerous lesions and esophageal cancer. Characteristic variations of the microbiome have potential application prospects in identifying and concentrating high-risk population of esophageal cancer. In our previous studies, we found that the abundance of Fusobacterium present different distributions between esophageal cancer tissues and adjacent non-tumor tissues. In addition, the diversity of oral microbiome gradually decreased with the progression of precancerous lesions of esophageal cancer. However, these findings still lacked the evidence on specific active strains and the confirmation of prospective study. This study is based on multi-center prospective cohort of high-risk areas of esophageal cancer. Firstly, a population-based case-control study is designed, combined with metagenomics and culturomics technology, to screen the specific active strains associated to esophageal cancer and precancerous lesions. The function of strains will be verified through animal experiments. Then a second follow-up will be conducted for the cohort. Based on the specific active strains of upper gastrointestinal tract, the prediction model of esophageal cancer and precancerous lesions will be constructed by logistic regression and random forest methods combined with environmental exposure factors. This study will provide evidence for the precise identification of high-risk population and the optimization of esophageal cancer screening strategy.