循环游离细菌DNA作为新型结直肠肿瘤筛查和早期诊断标志物的研究

我国结直肠癌发病率近年逐年上升，且总体生存率远落后于欧美。筛查和早期诊断结直肠肿瘤（癌和腺瘤）是降低发病率和改善预后的关键。现行初筛方案的灵敏度和依从性均严重不足，迫切需要更高效便捷的方法。课题组前期发现结直肠肿瘤及健康人的循环游离DNA中均有一定比例细菌DNA，基于其菌种分布及丰度差异采用随机森林模型建立的诊断模型，不仅准确筛选出结直肠癌，还能将常规初筛灵敏度较低的腺瘤也全部识别，提示循环游离细菌DNA是良好的生物标志物。本项目拟基于前期结直肠癌专病队列样本库，建立健康人、结直肠癌和腺瘤的循环游离细菌DNA数据库，进行模型扩大验证和优化；将其与常规初筛方法粪便潜血比较，明确灵敏度、特异度、总符合率、一致性系数等指标；同时探讨循环游离细菌DNA与临床特征的相关性，并对其来源进行解析。本研究有望为结直肠肿瘤筛查和早期诊断提供高灵敏度的新型血液标志物，为降低结直肠癌发病率、改善预后提供新方案。

The incidence of colorectal cancer in China is gradually increasing, and the overall survival is much worse than that of European and American countries. Improving early diagnosis of colorectal neoplasms including cancer and adenoma is the key strategy to reduce the incidence and improve the prognosis. The existing methods such as fecal occult blood are seriously insufficient in sensitivity and compliance, thus more convenient and efficient detection methods are urgently needed. Our previous study found that there was a certain proportion of bacterial DNA fragments in the circulating free DNA from patients with colorectal neoplasms and healthy people. Based on the difference of species distribution and abundance, the diagnostic model was established by random forest model. This model can not only accurately distinguish colorectal cancer, but also identifies all the adenomas which has the lowest sensitivity by current routine screening, suggesting that circulating free bacterial DNA is an excellent biomarker. Based on the "National Colorectal Cancer Cohort" established previously, this project aims to build a circulating free bacterial DNA database of healthy people and patients with colorectal adenoma or colorectal cancer, and to verify and optimize the colorectal neoplasms diagnostic model. Furthermore, we will assess the authenticity and reliability of the model by clarifing key indicators such as sensitivity, specificity, coincidence rate and consistency, and then compare it with standard screening method of fecal occult blood detection. Meanwhile, we will explore the correlation between circulating free bacterial DNA and clinical characteristics and analyze the source of circulating free bacterial DNA. This study is expected to provide a novel blood biomarker with extremely high sensitivity for colorectal tumor screening and early diagnosis, and to provide new solutions for reducing the incidence of colorectal cancer and improving prognosis.