超灵敏循环肿瘤DNA检测用于早期肺腺癌术前疾病分层
Ultrasensitive ctDNA detection for preoperative disease stratification in early-stage lung adenocarcinoma.
作者信息
Black James R M, Bartha Gabor, Abbott Charles W, Boyle Sean M, Karasaki Takahiro, Li Bailiang, Chen Rui, Harris Jason, Veeriah Selvaraju, Colopi Martina, Bakir Maise Al, Liu Wing Kin, Lyle John, Navarro Fábio C P, Northcott Josette, Pyke Rachel Marty, Hill Mark S, Thol Kerstin, Huebner Ariana, Bailey Chris, Colliver Emma C, Martínez-Ruiz Carlos, Grigoriadis Kristiana, Pawlik Piotr, Moore David A, Marinelli Daniele, Shutkever Oliver G, Murphy Cian, Sivakumar Monica, Shaw Jacqui A, Hackshaw Allan, McGranahan Nicholas, Jamal-Hanjani Mariam, Frankell Alexander M, Chen Richard O, Swanton Charles
机构信息
Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.
Cancer Evolution and Genome Instability Laboratory., The Francis Crick Institute, London, UK.
出版信息
Nat Med. 2025 Jan;31(1):70-76. doi: 10.1038/s41591-024-03216-y. Epub 2025 Jan 13.
Circulating tumor DNA (ctDNA) detection can predict clinical risk in early-stage tumors. However, clinical applications are constrained by the sensitivity of clinically validated ctDNA detection approaches. NeXT Personal is a whole-genome-based, tumor-informed platform that has been analytically validated for ultrasensitive ctDNA detection at 1-3 ppm of ctDNA with 99.9% specificity. Through an analysis of 171 patients with early-stage lung cancer from the TRACERx study, we detected ctDNA pre-operatively within 81% of patients with lung adenocarcinoma (LUAD), including 53% of those with pathological TNM (pTNM) stage I disease. ctDNA predicted worse clinical outcome, and patients with LUAD with <80 ppm preoperative ctDNA levels (the 95% limit of detection of a ctDNA detection approach previously published in TRACERx) experienced reduced overall survival compared with ctDNA-negative patients with LUAD. Although prospective studies are needed to confirm the clinical utility of the assay, these data show that our approach has the potential to improve disease stratification in early-stage LUADs.
循环肿瘤DNA（ctDNA）检测可预测早期肿瘤的临床风险。然而，临床应用受到经临床验证的ctDNA检测方法灵敏度的限制。NeXT Personal是一个基于全基因组、肿瘤信息导向的平台，已通过分析验证，可在ctDNA浓度为1 - 3 ppm时以99.9%的特异性进行超灵敏ctDNA检测。通过对TRACERx研究中的171例早期肺癌患者进行分析，我们在术前检测到81%的肺腺癌（LUAD）患者体内存在ctDNA，其中包括53%的病理TNM（pTNM）I期疾病患者。ctDNA预示着更差的临床结局，术前ctDNA水平<80 ppm（此前TRACERx发表的一种ctDNA检测方法的95%检测限）的LUAD患者与ctDNA阴性的LUAD患者相比，总生存期缩短。尽管需要前瞻性研究来证实该检测方法的临床实用性，但这些数据表明我们的方法有潜力改善早期LUAD的疾病分层。
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