研究發現肺癌中早期擴散的循環腫瘤細胞



本期文章:《自然—醫學》:Online/在線發表

英國曼徹斯特大學Caroline Dive、Ged Brady和倫敦大學學院Charles Swanton等研究人員合作,發現了出現在腫瘤切除和疾病復發前的肺靜脈循環腫瘤細胞擴散。相關論文2019年10月7日在線發表于《自然—醫學》。

研究人員介紹,約有50%接受根治性手術的早期非小細胞肺癌(NSCLC)患者將在5年內復發。手術時對循環腫瘤細胞(CTC)的檢測可能作為一種可用于識別復發風險較高的患者的工具,從而可建議對其進行更頻繁的監測。

研究人員希望了解在早期NSCLC手術切除中CellSearch檢測到的肺靜脈CTC(PV-CTC)是否代表引起隨后疾病復發的亞克隆。參與TRACERx研究的100名患者中有48%檢測到PV-CTC,與肺癌特異性復發相關,并且在針對腫瘤階段進行調整的多變量分析中,PV-CTC仍是復發的獨立預測因子。在一項案例研究中,在手術中收集到的單個PV-CTC的基因組分析顯示,與原發腫瘤(79%)相比,在10個月后發現的轉移灶中有更高的突變重疊(91%),這提示早期傳播的PV-CTC參與疾病復發??傊?,PV-CTC結果和基因組圖譜突顯了PV-CTC作為手術后NSCLC復發的早期預測指標的潛力。然而,PV-CTC在預測復發中有限的靈敏度表明,有必要使用更大的獨立研究隊列進行進一步的研究,以確認并更好地定義PV-CTC在早期NSCLC中的潛在臨床應用。

附:英文原文

Title: Pulmonary venous circulating tumor cell dissemination before tumor resection and disease relapse

Author: Francesca Chemi, Dominic G. Rothwell, Nicholas McGranahan, Sakshi Gulati, Chris Abbosh, Simon P. Pearce, Cong Zhou, Gareth A. Wilson, Mariam Jamal-Hanjani, Nicolai Birkbak, Jackie Pierce, Chang Sik Kim, Saba Ferdous, Deborah J. Burt, Daniel Slane-Tan, Fabio Gomes, David Moore, Rajesh Shah, Maise Al Bakir, Crispin Hiley, Selvaraju Veeriah, Yvonne Summers, Philip Crosbie, Sophia Ward, Barbara Mesquita, Marek Dynowski, Dhruva Biswas, Jonathan Tugwood, Fiona Blackhall, Crispin Miller, Allan Hackshaw, Ged Brady, Charles Swanton, Caroline Dive

Issue&Volume: 2019-10-07

Abstract: Approximately 50% of patients with early-stage non-small-cell lung cancer (NSCLC) who undergo surgery with curative intent will relapse within 5 years1,2. Detection of circulating tumor cells (CTCs) at the time of surgery may represent a tool to identify patients at higher risk of recurrence for whom more frequent monitoring is advised. Here we asked whether CellSearch-detected pulmonary venous CTCs (PV-CTCs) at surgical resection of early-stage NSCLC represent subclones responsible for subsequent disease relapse. PV-CTCs were detected in 48% of 100 patients enrolled into the TRACERx study3, were associated with lung-cancer-specific relapse and remained an independent predictor of relapse in multivariate analysis adjusted for tumor stage. In a case study, genomic profiling of single PV-CTCs collected at surgery revealed higher mutation overlap with metastasis detected 10 months later (91%) than with the primary tumor (79%), suggesting that early-disseminating PV-CTCs were responsible for disease relapse. Together, PV-CTC enumeration and genomic profiling highlight the potential of PV-CTCs as early predictors of NSCLC recurrence after surgery. However, the limited sensitivity of PV-CTCs in predicting relapse suggests that further studies using a larger, independent cohort are warranted to confirm and better define the potential clinical utility of PV-CTCs in early-stage NSCLC. Pulmonary venous tumor cells disseminating before tumor resection are heterogeneous, predict relapse and seed future metastasis of lung cancer

DOI: 10.1038/s41591-019-0593-1

Source:https://www.nature.com/articles/s41591-019-0593-1

期刊信息

Nature Medicine:《自然—醫學》,創刊于1995年。隸屬于施普林格·自然出版集團,最新IF:30.641
官方網址:https://www.nature.com/nm/
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