小柯机器人

英国伦敦大学学院Charles Swanton等研究人员合作揭示TRACERx中非小细胞肺癌转移的演变过程。这一研究成果于2023年4月12日在线发表在国际学术期刊《自然》上。

研究人员报告了对126个非小细胞肺癌（NSCLC）肿瘤的纵向演化分析，这些肿瘤来自于TRACERx的421名前瞻性招募的患者，他们发生了转移性疾病，并与144个非转移性肿瘤的对照组进行了比较。在25%的病例中，转移瘤在原发肿瘤的最后一次克隆扫荡之前就发生了早期分化，并且早期分化在最初诊断时是吸烟者的患者中富集起来。模拟表明，早期转移分化更经常发生在较小的肿瘤直径（小于8毫米）。单一区域的原发肿瘤取样导致83%的晚期分化病例被误判为早期，突出了广泛的原发肿瘤取样的重要性。32%的病例发现了与胸腔外疾病复发有关的多克隆传播。

在不到20%的病例中，原发淋巴结疾病促成了转移性复发，这代表了转移潜力的一个标志，而不是随后复发/疾病进展的途径。转移滋生的亚克隆在原发肿瘤内表现出亚克隆性的扩张，可能反映了正向的选择。这些研究结果强调了选择在未经治疗的原发肿瘤内转移性克隆演变中的重要性，在决定复发部位方面，单克隆与多克隆播种之间的区别，目前对早期分化肿瘤的放射学筛选方法的局限性，以及在复发前开发针对转移播种亚克隆的策略必要性。

附：英文原文

Title: The evolution of non-small cell lung cancer metastases in TRACERx

Author: Al Bakir, Maise, Huebner, Ariana, Martnez-Ruiz, Carlos, Grigoriadis, Kristiana, Watkins, Thomas B. K., Pich, Oriol, Moore, David A., Veeriah, Selvaraju, Ward, Sophia, Laycock, Joanne, Johnson, Diana, Rowan, Andrew, Razaq, Maryam, Akther, Mita, Naceur-Lombardelli, Cristina, Prymas, Paulina, Toncheva, Antonia, Hessey, Sonya, Dietzen, Michelle, Colliver, Emma, Frankell, Alexander M., Bunkum, Abigail, Lim, Emilia L., Karasaki, Takahiro, Abbosh, Christopher, Hiley, Crispin T., Hill, Mark S., Cook, Daniel E., Wilson, Gareth A., Salgado, Roberto, Nye, Emma, Stone, Richard Kevin, Fennell, Dean A., Price, Gillian, Kerr, Keith M., Naidu, Babu, Middleton, Gary, Summers, Yvonne, Lindsay, Colin R., Blackhall, Fiona H., Cave, Judith, Blyth, Kevin G., Nair, Arjun, Ahmed, Asia, Taylor, Magali N., Procter, Alexander James, Falzon, Mary, Lawrence, David, Navani, Neal, Thakrar, Ricky M., Janes, Sam M., Papadatos-Pastos, Dionysis, Forster, Martin D., Lee, Siow Ming, Ahmad, Tanya, Quezada, Sergio A., Peggs, Karl S., Van Loo, Peter

Issue&Volume: 2023-04-12

Abstract: Metastatic disease is responsible for the majority of cancer-related deaths1. We report the longitudinal evolutionary analysis of 126 non-small cell lung cancer (NSCLC) tumours from 421 prospectively recruited patients in TRACERx who developed metastatic disease, compared with a control cohort of 144 non-metastatic tumours. In 25% of cases, metastases diverged early, before the last clonal sweep in the primary tumour, and early divergence was enriched for patients who were smokers at the time of initial diagnosis. Simulations suggested that early metastatic divergence more frequently occurred at smaller tumour diameters (less than 8mm). Single-region primary tumour sampling resulted in 83% of late divergence cases being misclassified as early, highlighting the importance of extensive primary tumour sampling. Polyclonal dissemination, which was associated with extrathoracic disease recurrence, was found in 32% of cases. Primary lymph node disease contributed to metastatic relapse in less than 20% of cases, representing a hallmark of metastatic potential rather than a route to subsequent recurrences/disease progression. Metastasis-seeding subclones exhibited subclonal expansions within primary tumours, probably reflecting positive selection. Our findings highlight the importance of selection in metastatic clone evolution within untreated primary tumours, the distinction between monoclonal versus polyclonal seeding in dictating site of recurrence, the limitations of current radiological screening approaches for early diverging tumours and the need to develop strategies to target metastasis-seeding subclones before relapse.

DOI: 10.1038/s41586-023-05729-x

Source: https://www.nature.com/articles/s41586-023-05729-x

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