刘小龙循环肿瘤DNA(ctDNA)检测策略及临床意义剖析.ppt

* * We used digital polymerase chain reaction – based technologies to evaluate the ability of circulating tumor DNA (ctDNA) to detect tumors in 640 patients with various cancer types. * * * * * * * Percentage of bins showing hypomethylation in HCC patients and chronic hepatitis B virus (HBV) carriers with cirrhosis (A). ROC curves for HCC patient detection using hypomethylation (B) and CNA (C) analyses. The P values shown are for the comparisons between using all sequenced reads from one lane and using 10 million reads. Our cohort of 388 patients with primary breast cancer before chemotherapy was selected from a multicenter study (SUCCESS). Postoperative plasma was fractionated in low- and high- molecular weight DNA by two different column systems. In both fractions, LOH was determined by a PCR- based microsatellite analysis using a panel of 8 polymorphic markers. Circulating tumor DNA in plasma from 30 patients after chemotherapy was additionally analyzed. The signi?cance levels were adjusted for multiple comparisons. The improved detection of LOH on cell-free DNA provides important information on DNA losses of tumor suppressor genes TIG1, PTEN, cyclin D2, RB1, and BRCA1 in breast cancer. * cirDNA was fractionated into high- and low molecular-weight fraction (HMWF, LMWF) for LOH-profiling,utilizing PCR-based fluorescence microsatellite analysis. BM aspirates w * Comparison of Circulating Tumor DNA, CA 15-3, and Circulating Tumor Cells as Blood-Based Biomarkers 灵敏度： 偱环肿瘤DNA：85% CA 15-3：59% 灵敏度： 偱环肿瘤DNA：90% 偱环肿瘤细胞：67% Comparison of Circulating Biomarkers to Monitor Tumor Dynamics and Predict Survival. 结论：相对于蛋白类诊断标志物CA15-3及血液中的偱环肿瘤细胞，ctDNA在监测肿瘤的动态发展中具有更高的灵敏度。 血浆中ctDNA的含量与预后密切相关，含量越高，病人的5年生存率越低（P0.001）。 ctDNA含量的增高及CTC数目的增加，病人的预后显著变差，而CA15-3没有预后判断功能。 监测ctDNA的突变率比监测cfDNA浓度，对胃癌动态发展的监控灵敏度更高。 利用区域捕获测序技术检测乳腺癌原发瘤及肝脏转移瘤的基因突变情况，并监控血液中ctDNA在治疗过程中的动态变化。 ctDNA在监测肿瘤的动态发展中具有更高的灵敏度和特异性； ctDNA能比蛋白类标志物CA15.3更早的预测肿瘤动态发展情况。 相对于传统的影像学及蛋白类血清标志物，通过评估ctDNA的突变频率能更早、更准确的预测结肠癌患者肿瘤经治