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文献精选 > 近年高分"液体活检"研究（IF≥30，近5年）

Exosome-based liquid biopsies in cancer: opportunities and challenges. ​

文献信息 ​

DOI10.1016/j.annonc.2021.01.074
PMID33548389
期刊Annals of oncology : official journal of the European Society for Medical Oncology
影响因子65.4
JCR 分区Q1
发表年份2021
被引次数413
关键词无细胞DNA（cfDNA）, 循环肿瘤DNA（ctDNA）, 循环肿瘤细胞（CTC）, 外泌体, 细胞外囊泡
文献类型Journal Article, Research Support, N.I.H., Extramural, Review
ISSN0923-7534
页码466-477
期号32(4)
作者W Yu, J Hurley, D Roberts, S K Chakrabortty, D Enderle, M Noerholm, X O Breakefield, J K Skog

一句话小结 ​

液体活检在癌症研究中逐渐崭露头角，尤其是外泌体作为潜在的生物标志物，能够提供肿瘤细胞释放的遗传和分子信息。研究表明，基于外泌体的检测方法在早期癌症筛查和临床决策中具有重要应用价值，已被纳入相关的临床指南中。

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无细胞DNA（cfDNA） · 循环肿瘤DNA（ctDNA） · 循环肿瘤细胞（CTC） · 外泌体 · 细胞外囊泡

摘要 ​

液体活检在癌症研究中获得了重要进展，并在多种应用中正经历快速发展。当前，利用液体活检进行癌症早期检测、治疗分层、残余疾病和复发监测的努力正在显著增加。尽管大多数研究集中在循环肿瘤细胞和循环肿瘤DNA的应用上，但外泌体和其他细胞外囊泡作为一种潜在的更广泛和互补的应用平台也逐渐受到关注。外泌体/细胞外囊泡是细胞（包括癌细胞）释放到周围生物液体中的小囊泡。这些外泌体包含来自肿瘤的材料，如DNA、RNA、蛋白质、脂质、糖结构和代谢物。此外，外泌体表面携带的分子提供了有关其来源的线索，使得能够对囊泡类型进行分类，并从特定组织来源中富集标志物。外泌体是细胞间通信系统的一部分，癌细胞通常利用它们作为生物信使，从中获益以促进其生长。由于外泌体是疾病过程的一部分，因此它们在生物标志物研究中引起了极大的关注。外泌体在生物液体（如血浆和尿液）中极为稳定，即使在疾病早期阶段也可以被分离用于临床评估。基于外泌体的生物标志物迅速被应用于临床，首个基于外泌体RNA的前列腺癌检测已经帮助超过50,000名患者进行决策，并已被纳入国家综合癌症网络的早期前列腺癌检测指南中。本文将讨论基于外泌体的液体活检在肿瘤生物标志物和临床实施中的优势与挑战，特别是在循环肿瘤DNA和循环肿瘤细胞的背景下。

英文摘要 ​

Liquid biopsy in cancer has gained momentum in clinical research and is experiencing a boom for a variety of applications. There are significant efforts to utilize liquid biopsies in cancer for early detection and treatment stratification, as well as residual disease and recurrence monitoring. Although most efforts have used circulating tumor cells and circulating tumor DNA for this purpose, exosomes and other extracellular vesicles have emerged as a platform with potentially broader and complementary applications. Exosomes/extracellular vesicles are small vesicles released by cells, including cancer cells, into the surrounding biofluids. These exosomes contain tumor-derived materials such as DNA, RNA, protein, lipid, sugar structures, and metabolites. In addition, exosomes carry molecules on their surface that provides clues regarding their origin, making it possible to sort vesicle types and enrich signatures from tissue-specific origins. Exosomes are part of the intercellular communication system and cancer cells frequently use them as biological messengers to benefit their growth. Since exosomes are part of the disease process, they have become of tremendous interest in biomarker research. Exosomes are remarkably stable in biofluids, such as plasma and urine, and can be isolated for clinical evaluation even in the early stages of the disease. Exosome-based biomarkers have quickly become adopted in the clinical arena and the first exosome RNA-based prostate cancer test has already helped >50 000 patients in their decision process and is now included in the National Comprehensive Cancer Network guidelines for early prostate cancer detection. This review will discuss the advantages and challenges of exosome-based liquid biopsies for tumor biomarkers and clinical implementation in the context of circulating tumor DNA and circulating tumor cells.

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主要研究问题 ​

  1. 在使用外泌体进行液体活检时，存在哪些技术挑战和解决方案？
  2. 外泌体与循环肿瘤细胞和循环肿瘤DNA相比，具有哪些独特的优势？
  3. 外泌体在不同类型癌症中的应用潜力如何，是否存在特定的癌症类型更适合这种方法？
  4. 外泌体作为生物标志物在临床决策中的实际应用案例有哪些，成功率如何？
  5. 未来的研究方向是什么，以推动外泌体液体活检技术的发展和临床应用？

核心洞察 ​

研究背景和目的 ​

液体活检在癌症临床研究中逐渐受到重视，主要用于早期检测、治疗分层以及监测残余疾病和复发。尽管目前大多数研究集中在循环肿瘤细胞（CTCs）和循环肿瘤DNA（ctDNA）上，外泌体（exosomes）及其他细胞外囊泡（extracellular vesicles, EVs）作为一种潜在的生物标志物平台，展现出更广泛的应用前景。本文旨在探讨基于外泌体的液体活检在肿瘤生物标志物及临床实施中的优势与挑战。

主要方法/材料/实验设计 ​

研究主要分为以下几个步骤：

  1. 液体活检的分类：

    • ctDNA：来源于死亡肿瘤细胞，反映肿瘤基因组状态。
    • CTCs：完整的肿瘤细胞，能够提供肿瘤的生物学特征。
    • 外泌体：由活细胞分泌，携带多种生物分子（如RNA、DNA、蛋白质），反映肿瘤细胞的状态。

  2. 外泌体的分离与分析：

    • 通过特定表面标记物富集外泌体。
    • 结合多种分析技术（如RNA测序、蛋白质组学）进行综合评估。

  3. 临床应用：

    • 使用外泌体RNA与ctDNA联合检测，提高突变检测的灵敏度。
Mermaid diagram

关键结果和发现 ​

  1. 外泌体的优势：

    • 稳定性强，能够在早期疾病阶段被分离并用于临床评估。
    • 可通过表面标记物进行富集，提高检测的特异性和灵敏度。

  2. 联合检测的效果：

    • 外泌体RNA与ctDNA联合使用时，检测突变的灵敏度显著提高。
    • 在早期癌症检测中，外泌体能够提供更丰富的生物标志物信息。

主要结论/意义/创新性 ​

外泌体作为液体活检的一部分，展现出独特的临床价值。它们不仅提供了多种生物分子信息，还能通过与ctDNA的联合分析提高肿瘤检测的准确性。这一研究为液体活检的临床应用提供了新的视角和可能性，尤其在癌症早期检测和监测方面具有重要意义。

研究局限性和未来方向 ​

  1. 局限性：

    • 外泌体的富集和分析技术尚需进一步优化，以提高操作的标准化和 reproducibility。
    • 临床应用的验证需要更多大规模的前瞻性研究。

  2. 未来方向：

    • 继续探索外泌体在不同类型癌症中的生物标志物潜力。
    • 开发便携式的外泌体分析设备，以促进临床应用的普及。

参考文献 ​

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  2. Assessment of EGFR mutations in circulating tumor cell preparations from NSCLC patients by next generation sequencing: toward a real-time liquid biopsy for treatment. - Antonio Marchetti;Maela Del Grammastro;Lara Felicioni;Sara Malatesta;Giampaolo Filice;Irene Centi;Tommaso De Pas;Armando Santoro;Antonio Chella;Alba Ariela Brandes;Paola Venturino;Franco Cuccurullo;Lucio Crinò;Fiamma Buttitta - PloS one (2014)
  3. Circulating tumor cells, disease progression, and survival in metastatic breast cancer. - Massimo Cristofanilli;G Thomas Budd;Matthew J Ellis;Alison Stopeck;Jeri Matera;M Craig Miller;James M Reuben;Gerald V Doyle;W Jeffrey Allard;Leon W M M Terstappen;Daniel F Hayes - The New England journal of medicine (2004)
  4. Microfluidic devices to enrich and isolate circulating tumor cells. - J H Myung;S Hong - Lab on a chip (2015)
  5. The patterns and dynamics of genomic instability in metastatic pancreatic cancer. - Peter J Campbell;Shinichi Yachida;Laura J Mudie;Philip J Stephens;Erin D Pleasance;Lucy A Stebbings;Laura A Morsberger;Calli Latimer;Stuart McLaren;Meng-Lay Lin;David J McBride;Ignacio Varela;Serena A Nik-Zainal;Catherine Leroy;Mingming Jia;Andrew Menzies;Adam P Butler;Jon W Teague;Constance A Griffin;John Burton;Harold Swerdlow;Michael A Quail;Michael R Stratton;Christine Iacobuzio-Donahue;P Andrew Futreal - Nature (2010)
  6. Circulating tumor cells predict survival benefit from treatment in metastatic castration-resistant prostate cancer. - Johann S de Bono;Howard I Scher;R Bruce Montgomery;Christopher Parker;M Craig Miller;Henk Tissing;Gerald V Doyle;Leon W W M Terstappen;Kenneth J Pienta;Derek Raghavan - Clinical cancer research : an official journal of the American Association for Cancer Research (2008)
  7. Glioblastoma microvesicles transport RNA and proteins that promote tumour growth and provide diagnostic biomarkers. - Johan Skog;Tom Würdinger;Sjoerd van Rijn;Dimphna H Meijer;Laura Gainche;Miguel Sena-Esteves;William T Curry;Bob S Carter;Anna M Krichevsky;Xandra O Breakefield - Nature cell biology (2008)
  8. Molecular Detection and Analysis of Exosomes Using Surface-Enhanced Raman Scattering Gold Nanorods and a Miniaturized Device. - Elyahb Allie Kwizera;Ryan O'Connor;Vojtech Vinduska;Melody Williams;Elizabeth R Butch;Scott E Snyder;Xiang Chen;Xiaohua Huang - Theranostics (2018)
  9. Magnetic bead-based isolation of exosomes. - Morten P Oksvold;Axl Neurauter;Ketil W Pedersen - Methods in molecular biology (Clifton, N.J.) (2015)
  10. Urinary Exosomal and cell-free DNA Detects Somatic Mutation and Copy Number Alteration in Urothelial Carcinoma of Bladder. - Dong Hyeon Lee;Hana Yoon;Sanghui Park;Jeong Seon Kim;Young-Ho Ahn;Kihwan Kwon;Donghwan Lee;Kwang Hyun Kim - Scientific reports (2018)

引用本文的文献 ​

  1. EVs from BALF-Mediators of Inflammation and Potential Biomarkers in Lung Diseases. - Lukasz Zareba;Jacek Szymanski;Zuzanna Homoncik;Malgorzata Czystowska-Kuzmicz - International journal of molecular sciences (2021)
  2. Towards Novel Non-Invasive Colorectal Cancer Screening Methods: A Comprehensive Review. - Allegra Ferrari;Isabelle Neefs;Sarah Hoeck;Marc Peeters;Guido Van Hal - Cancers (2021)
  3. The Role of Extracellular Vesicles in the Progression of Human Neuroblastoma. - Danilo Marimpietri;Irma Airoldi;Angelo Corso Faini;Fabio Malavasi;Fabio Morandi - International journal of molecular sciences (2021)
  4. Liquid Biomarkers for Improved Diagnosis and Classification of CNS Tumors. - Severa Bunda;Jeffrey A Zuccato;Mathew R Voisin;Justin Z Wang;Farshad Nassiri;Vikas Patil;Sheila Mansouri;Gelareh Zadeh - International journal of molecular sciences (2021)
  5. The role and application of small extracellular vesicles in gastric cancer. - Hao Wu;Mengdi Fu;Jin Liu;Wei Chong;Zhen Fang;Fengying Du;Yang Liu;Liang Shang;Leping Li - Molecular cancer (2021)
  6. Circulating Exosomal MiR-107 Restrains Tumorigenesis in Diffuse Large B-Cell Lymphoma by Targeting 14-3-3η. - Jiarui Liu;Yang Han;Shunfeng Hu;Yiqing Cai;Juan Yang;Shuai Ren;Yi Zhao;Tiange Lu;Xiangxiang Zhou;Xin Wang - Frontiers in cell and developmental biology (2021)
  7. Exosome Traceability and Cell Source Dependence on Composition and Cell-Cell Cross Talk. - Rabab N Hamzah;Karrer M Alghazali;Alexandru S Biris;Robert J Griffin - International journal of molecular sciences (2021)
  8. Urine as a Source of Liquid Biopsy for Cancer. - Masanori Oshi;Vijayashree Murthy;Hideo Takahashi;Michelle Huyser;Maiko Okano;Yoshihisa Tokumaru;Omar M Rashid;Ryusei Matsuyama;Itaru Endo;Kazuaki Takabe - Cancers (2021)
  9. Identification of MicroRNAs as Viable Aggressiveness Biomarkers for Prostate Cancer. - Luis Javier Martínez-González;Victor Sánchez-Conde;Jose María González-Cabezuelo;Alba Antunez-Rodríguez;Eduardo Andrés-León;Inmaculada Robles-Fernandez;Jose Antonio Lorente;Fernando Vázquez-Alonso;María Jesus Alvarez-Cubero - Biomedicines (2021)
  10. Understanding the Pathophysiology of Exosomes in Schistosomiasis: A New Direction for Disease Control and Prevention. - Yue Yuan;Jianping Zhao;Min Chen;Huifang Liang;Xin Long;Bixiang Zhang;Xiaoping Chen;Qian Chen - Frontiers in immunology (2021)

... (403 更多 篇文献)

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