目前传统肿瘤标志物用于肿瘤早诊及预后评估的临床效果并不理想。近年来，液体活检技术在新型肿瘤标志物临床应用中取得突破性进展。其中，核基因组ctDNA检测发展最为迅猛。但因其外周血中丰度低，检测技术要求高，导致目前常见方案临床效果无法令人满意。线粒体DNA（mtDNA）具有高突变率、高拷贝数和检测成本低的独特优势，有望成为更理想的液体活检新型标志物。基于项目组自主研发的新型双barcode文库构建以及mtDNA捕获等专利技术，本项目拟解决以下关键问题：1.肿瘤患者血浆游离mtDNA含量及突变的精准检测方法？肿瘤发生发展不同阶段血浆游离mtDNA含量及突变的个体差异及特征图谱？2.基于血浆游离mtDNA多重标志物检测及机器学习技术，如何构建肿瘤早诊及预后预测模型？其临床价值如何？本项目的完成将为推进血浆游离mtDNA相关多重肿瘤标志物临床检验应用奠定理论和技术基础。

At present，traditional tumor biomarkers are not ideal for tumor early diagnosis and prognostic evaluation。In recent years, liquid biopsy has made breakthrough progress in the clinical application of novel tumor biomarkers. Among all the liquid biopsy methods, ctDNA detection is in most rapidly progress. However, because of its low abundance in plasma and high requirements of detection technology, the clinical efficacy of the current common protocols is not satisfying. Considering its high mutation rate and high copy number, mitochondrial DNA (mtDNA) is relatively easy to be detected and expected to be a novel ideal biomarker for liquid biopsy. Based on our patent technology for dual-barcode related library construction and mtDNA capture, the project is planned to solve the following theoretical and technical problems: 1. How to establish the method to accurately detect plasma cell-free mtDNA content and mutation in tumor patients? What is the individual differences and profiling of plasma cell-free mtDNA content and mutation in the different stages of tumorigenesis and progression? 2. How to construct and evaluate the clinical models for tumor early diagnosis and prognosis prediction based on the detection of multiple markers of cell free mtDNA by the machine learning? The completion of this project will lay the theoretical and technical foundation for the clinical application of cell free mtDNA-related multiple biomarkers.