Sensitive and specific multi-cancer detection and localization using methylation signatures in cell-free DNA.
Sensitive and specific multi-cancer detection and localization using methylation signatures in cell-free DNA.
复制标题
DOI：
10.1016/j.annonc.2020.02.011
复制
发表时间：
2020-06
期刊：
影响因子：
--
通讯作者：
CCGA Consortium
中科院分区：
文献类型：
--
作者：
Liu MC;Oxnard GR;Klein EA;Swanton C;Seiden MV;CCGA Consortium
早期癌症检测可以在结果更好、治疗更少病态的时候识别出肿瘤。这项前瞻性病例对照亚研究（来自NCT02889978和NCT03085888）评估了循环游离DNA （cfDNA）靶向甲基化分析的性能，以高特异性检测和定位所有阶段的多种癌症类型。6689名参与者[2482种癌症（bb50种癌症类型），4207种非癌症]被分为训练组和验证组。血浆cfDNA进行亚硫酸盐测序，靶向一组bb10万信息丰富的甲基化区域。开发并验证了一种用于癌症检测和起源组织定位的分类器。训练集和验证集的性能是一致的。在验证中，特异性为99.3%[95%置信区间（CI）： 98.3% ~ 99.8%；0.7%假阳性率（FPR）]。在预先指定的12种癌症类型（肛门、膀胱、结肠/直肠、食道、头颈、肝脏/胆管、肺、淋巴瘤、卵巢、胰腺、浆细胞肿瘤、胃）中，I-III期敏感性为67.3% (CI: 60.7%至73.3%)，占美国每年癌症死亡人数的63%，所有癌症类型的敏感性为43.9% （CI: 39.4%至48.5%）。检测阶段的增加而增加:在预先确定的癌症类型的敏感性为39% (52% CI: 27%)在I期,69% (80% CI: 56%)在第二阶段中,83% (90% CI: 75%)在第三阶段,和92% (96% CI: 86%)在第四阶段。在所有癌症类型的敏感性为18% (25% CI: 13%)在I期,43% (51% CI: 35%)在第二阶段中,81% (87% CI: 73%)在第三阶段,和93% (96% CI: 87%)在四期,也是预测在96%的样品类似癌症信号;其中，TOO定位准确率为93%。cfDNA测序利用信息丰富的甲基化模式检测到50多种不同阶段的癌症类型。考虑到早期发现致命恶性肿瘤的潜在价值，在前瞻性人群水平研究中进一步评估该检测是合理的。
Early cancer detection could identify tumors at a time when outcomes are superior and treatment is less morbid. This prospective case-control sub-study (from NCT02889978 and NCT03085888) assessed the performance of targeted methylation analysis of circulating cell-free DNA (cfDNA) to detect and localize multiple cancer types across all stages at high specificity. The 6689 participants [2482 cancer (>50 cancer types), 4207 non-cancer] were divided into training and validation sets. Plasma cfDNA underwent bisulfite sequencing targeting a panel of >100 000 informative methylation regions. A classifier was developed and validated for cancer detection and tissue of origin (TOO) localization. Performance was consistent in training and validation sets. In validation, specificity was 99.3% [95% confidence interval (CI): 98.3% to 99.8%; 0.7% false-positive rate (FPR)]. Stage I–III sensitivity was 67.3% (CI: 60.7% to 73.3%) in a pre-specified set of 12 cancer types (anus, bladder, colon/rectum, esophagus, head and neck, liver/bile-duct, lung, lymphoma, ovary, pancreas, plasma cell neoplasm, stomach), which account for ~63% of US cancer deaths annually, and was 43.9% (CI: 39.4% to 48.5%) in all cancer types. Detection increased with increasing stage: in the pre-specified cancer types sensitivity was 39% (CI: 27% to 52%) in stage I, 69% (CI: 56% to 80%) in stage II, 83% (CI: 75% to 90%) in stage III, and 92% (CI: 86% to 96%) in stage IV. In all cancer types sensitivity was 18% (CI: 13% to 25%) in stage I, 43% (CI: 35% to 51%) in stage II, 81% (CI: 73% to 87%) in stage III, and 93% (CI: 87% to 96%) in stage IV. TOO was predicted in 96% of samples with cancer-like signal; of those, the TOO localization was accurate in 93%. cfDNA sequencing leveraging informative methylation patterns detected more than 50 cancer types across stages. Considering the potential value of early detection in deadly malignancies, further evaluation of this test is justified in prospective population-level studies.
登录
查看更多内容
影响因子：
3.8
作者：
Narayan, Anand;Fischer, Alexander;Harvey, Susan
通讯作者：
Harvey, Susan
影响因子：
19.7
作者：
Lehman, Constance D.;Arao, Robert F.;Miglioretti, Diana L.
通讯作者：
Miglioretti, Diana L.
影响因子：
17.1
作者：
Leary RJ;Sausen M;Kinde I;Papadopoulos N;Carpten JD;Craig D;O'Shaughnessy J;Kinzler KW;Parmigiani G;Vogelstein B;Diaz LA Jr;Velculescu VE
通讯作者：
Velculescu VE
影响因子：
64.8
作者：
Shen, Shu Yi;Singhania, Rajat;De Carvalho, Daniel D.
通讯作者：
De Carvalho, Daniel D.
DOI：
10.1126/science.1235122
发表时间：
2013-03-29
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Vogelstein B;Papadopoulos N;Velculescu VE;Zhou S;Diaz LA Jr;Kinzler KW
通讯作者：
Kinzler KW