小柯机器人

英国伦敦大学学院Christopher Abbosh等研究人员利用ctDNA跟踪TRACERx中的早期肺癌转移性传播。相关论文于2023年4月13日在线发表于国际学术期刊《自然》。

研究人员开发了循环肿瘤DNA（ctDNA）方法，跟踪在切除的非小细胞肺癌（NSCLC组织中发现的200个突变的中位数，这些突变收集自TRACERx研究2中的197名患者的1069个血浆样本。术前ctDNA检测的缺乏，区分了生物学上不活跃的肺腺癌和良好的临床结果。术后的血浆分析是在标准的放射学监测和实施细胞毒辅助治疗的背景下进行的。对术后120天内收集的血浆样本进行地标分析，发现25%的患者检测到ctDNA，包括49%的临床复发患者；3至6个月的ctDNA监测发现另外20%的地标阴性患者的疾病即将复发。

研究人员开发了一种生物信息学工具（ECLIPSE），用于在低ctDNA水平上对亚克隆结构进行非侵入性追踪。ECLIPSE确定了具有多克隆转移性传播的患者，这与不良的临床结果有关。通过测量术前血浆中的亚克隆癌细胞部分，研究人员发现，与非转移性亚克隆相比，播种未来转移的亚克隆明显更膨胀。这些发现将支持（新）辅助试验的进展，并利用低ctDNA水平的液体活检深入了解转移扩散的过程。

据介绍，ctDNA可用于检测和分析治愈性治疗后持续存在的残余肿瘤细胞。为了确定ctDNA作为早期NSCLC复发的系统性生物标志物的作用，需要对大型患者队列进行研究，包括纵向血浆采样和延长随访。

附：英文原文

Title: Tracking early lung cancer metastatic dissemination in TRACERx using ctDNA

Author: Abbosh, Christopher, Frankell, Alexander M., Harrison, Thomas, Kisistok, Judit, Garnett, Aaron, Johnson, Laura, Veeriah, Selvaraju, Moreau, Mike, Chesh, Adrian, Chaunzwa, Tafadzwa L., Weiss, Jakob, Schroeder, Morgan R., Ward, Sophia, Grigoriadis, Kristiana, Shahpurwalla, Aamir, Litchfield, Kevin, Puttick, Clare, Biswas, Dhruva, Karasaki, Takahiro, Black, James R. M., Martnez-Ruiz, Carlos, Bakir, Maise Al, Pich, Oriol, Watkins, Thomas B. K., Lim, Emilia L., Huebner, Ariana, Moore, David A., Godin-Heymann, Nadia, LHernault, Anne, Bye, Hannah, Odell, Aaron, Roberts, Paula, Gomes, Fabio, Patel, Akshay J., Manzano, Elizabeth, Hiley, Crispin T., Carey, Nicolas, Riley, Joan, Cook, Daniel E., Hodgson, Darren, Stetson, Daniel, Barrett, J. Carl, Kortlever, Roderik M., Evan, Gerard I., Hackshaw, Allan, Daber, Robert D., Shaw, Jacqui A., Aerts, Hugo J. W. L., Licon, Abel, Stahl, Josh, Jamal-Hanjani, Mariam, Birkbak, Nicolai J., McGranahan, Nicholas, Swanton, Charles

Issue&Volume: 2023-04-13

Abstract: Circulating tumour DNA (ctDNA) can be used to detect and profile residual tumour cells persisting after curative intent therapy1. The study of large patient cohorts incorporating longitudinal plasma sampling and extended follow-up is required to determine the role of ctDNA as a phylogenetic biomarker of relapse in early-stage non-small-cell lung cancer (NSCLC). Here we developed ctDNA methods tracking a median of 200 mutations identified in resected NSCLC tissue across 1,069 plasma samples collected from 197 patients enrolled in the TRACERx study2. A lack of preoperative ctDNA detection distinguished biologically indolent lung adenocarcinoma with good clinical outcome. Postoperative plasma analyses were interpreted within the context of standard-of-care radiological surveillance and administration of cytotoxic adjuvant therapy. Landmark analyses of plasma samples collected within 120days after surgery revealed ctDNA detection in 25% of patients, including 49% of all patients who experienced clinical relapse; 3 to 6 monthly ctDNA surveillance identified impending disease relapse in an additional 20% of landmark-negative patients. We developed a bioinformatic tool (ECLIPSE) for non-invasive tracking of subclonal architecture at low ctDNA levels. ECLIPSE identified patients with polyclonal metastatic dissemination, which was associated with a poor clinical outcome. By measuring subclone cancer cell fractions in preoperative plasma, we found that subclones seeding future metastases were significantly more expanded compared with non-metastatic subclones. Our findings will support (neo)adjuvant trial advances and provide insights into the process of metastatic dissemination using low-ctDNA-level liquid biopsy.

DOI: 10.1038/s41586-023-05776-4

Source: https://www.nature.com/articles/s41586-023-05776-4

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