基于前瞻性人群队列的食管癌早期预警生物标志物筛选及风险预测研究

我国是食管癌高发国，临床病例发现晚、预后差。筛选有预警能力的生物标志物组合，构建发病风险预测模型，实现高危个体识别与精准筛查，是食管癌防控的重要突破口。既往食管癌生物标记物研究多为基于医院开展的小样本回顾性病例对照研究设计，结果“碎片化”，结论可靠性与临床应用受限。本研究拟基于已在高发区建立的前瞻性自然人群队列（4.2万人，3断面内镜筛查、14年随访），通过“巢式病例对照”与“病例队列”两阶段串联设计，首次在同一人群、同一研究平台，前瞻性评价“口腔微生物”、“血清肿瘤相关抗原”、“遗传易感基因多态”三类生物标记物对食管癌发病风险的预警作用，联合宏观食管癌危险因素系统构建“基于生物标志物的食管癌风险预测模型与精准筛查策略”并进行人群验证与应用。最终实现降低筛查资源投入，提高防治效果的目标，助推我国食管癌防控工作的精准化与个体化进程。

China has the highest incidence rate of esophageal squamous cell carcinoma (ESCC) in the world. Most ESCC cases are at an advanced stage at the time of diagnosis with unfavorable prognosis. Constructing a valid risk prediction model for ESCC based on comprehensive evaluation of early warning abilities of biomarkers and precise identification of high-risk individuals from general population would be a crucial breakthrough in ESCC prevention and control. Most previous reports on esophageal cancer biomarkers were small- or medium-sized retrospective studies. “Low-level” sampling methods were employed and biomarkers were “fragmentally" evaluated in these studies, which have notably limited the reliability and clinical application of their results. This study is based on a population-level prospective esophageal cancer cohort (42,000 people, 14-year follow-up, 3 rounds of endoscopic screenings) established in high-risk area of esophageal cancer. Through a “two-stage design” including "nested case-control" and "case-cohort" study. This project will, for the first time, prospectively evaluate the early warning ability of biomarker panels incorporating oral microbes, serum tumor-associated antigens and genetic susceptibility polymorphism for predicting esophageal cancer risk in one population and on a uniform research platform. We will establish, validate and apply the "Biomarker-based precise screening technology and intervention strategy for esophageal cancer prevention and control”, which will substantially improve the overall effectiveness of esophageal cancer prevention in China and promote the entire process of precision prevention and control for esophageal cancer in China.