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Circulating tumor DNA: a promising biomarker in the liquid biopsy of cancer. ​

文献信息 ​

DOI10.18632/oncotarget.9453
PMID27223063
期刊Oncotarget
发表年份2016
被引次数197
关键词生物学, 生物标志物, 循环肿瘤DNA, 液体活检, 靶向治疗
文献类型Journal Article, Review
ISSN1949-2553
页码48832-48841
期号7(30)
作者Feifei Cheng, Li Su, Cheng Qian

一句话小结 ​

本研究回顾了循环肿瘤DNA（ctDNA）的生物学特性及其在癌症诊断和监测中的应用，指出ctDNA分析在检测遗传突变方面具有高敏感性和特异性，能够有效评估肿瘤进展及预后，并为靶向治疗提供支持。研究表明，ctDNA作为液体活检的方法有望显著改善传统组织活检在癌症管理中的局限性，推动早期检测和个体化治疗的发展。

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生物学 · 生物标志物 · 循环肿瘤DNA · 液体活检 · 靶向治疗

摘要 ​

组织活检是癌症的标准诊断程序，同时也提供了用于基因分型的材料，这有助于癌症的靶向治疗。然而，由于肿瘤的异质性和演变，基于组织活检的癌症诊断程序在评估癌症发展、预后和基因分型方面存在局限性。循环肿瘤DNA（ctDNA）是由肿瘤细胞释放到血液中的单链或双链DNA，因此它包含了原始肿瘤的突变。近年来，基于ctDNA分析的液体活检为癌症的分子诊断和监测开辟了新的视角。研究发现，使用ctDNA筛查遗传突变具有很高的敏感性和特异性，这表明ctDNA分析可能显著改善当前的肿瘤诊断系统，甚至促进早期检测。此外，ctDNA分析能够准确确定肿瘤的进展、预后，并协助进行靶向治疗。因此，使用ctDNA作为液体活检可能为肿瘤管理带来革命性的变化。在此，我们回顾了ctDNA的生物学特性、检测方法及其在肿瘤诊断、治疗和预后中的潜在应用。

英文摘要 ​

Tissue biopsy is the standard diagnostic procedure for cancers and also provides a material for genotyping, which can assist in the targeted therapies of cancers. However, tissue biopsy-based cancer diagnostic procedures have limitations in their assessment of cancer development, prognosis and genotyping, due to tumor heterogeneity and evolution. Circulating tumor DNA (ctDNA) is single- or double-stranded DNA released by the tumor cells into the blood and it thus harbors the mutations of the original tumor. In recent years, liquid biopsy based on ctDNA analysis has shed a new light on the molecular diagnosis and monitoring of cancer. Studies found that the screening of genetic mutations using ctDNA is highly sensitive and specific, suggesting that ctDNA analysis may significantly improve current systems of tumor diagnosis, even facilitating early-stage detection. Moreover, ctDNA analysis is capable of accurately determining the tumor progression, prognosis and assisting in targeted therapy. Therefore, using ctDNA as a liquid biopsy may herald a revolution for tumor management. Herein, we review the biology of ctDNA, its detection methods and potential applications in tumor diagnosis, treatment and prognosis.

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主要研究问题 ​

  1. ctDNA在不同类型癌症中的敏感性和特异性有何差异？
  2. 如何评估ctDNA分析在临床应用中的经济性和可行性？
  3. ctDNA检测技术的最新进展有哪些，未来的发展趋势如何？
  4. 在个体化治疗中，ctDNA如何影响治疗决策和疗效监测？
  5. 除了ctDNA，液体活检还有哪些其他生物标志物的应用潜力？

核心洞察 ​

研究背景和目的 ​

组织活检是癌症诊断的标准程序，但由于肿瘤异质性和演变，组织活检在癌症发展、预后和基因分型的评估中存在许多局限性。循环肿瘤DNA（ctDNA）是肿瘤细胞释放到血液中的单链或双链DNA，承载着原始肿瘤的突变信息。近年来，基于ctDNA分析的液体活检为癌症的分子诊断和监测提供了新的视角。本研究旨在综述ctDNA的生物学特性、检测方法及其在肿瘤诊断、治疗和预后中的潜在应用。

主要方法/材料/实验设计 ​

本研究主要采用文献综述的方式，综合分析ctDNA的生物学特性、检测技术及其在临床中的应用。具体流程如下：

Mermaid diagram

  1. ctDNA生物学特性：ctDNA的来源包括凋亡或坏死的肿瘤细胞、活的肿瘤细胞和循环肿瘤细胞（CTC）。ctDNA的大小和形式尚不明确，但通常显示出与肿瘤相关的分子特征。

  2. 检测方法：传统的Sanger测序方法在灵敏度和通量上存在局限，近年来，基于下一代测序（NGS）技术的检测方法（如BEAMing和CAPP-seq）显示出更高的灵敏度和特异性。

关键结果和发现 ​

  1. 灵敏度和特异性：ctDNA在早期癌症检测中的灵敏度高达97%，明显优于传统的血清肿瘤标志物（如CA15-3等）。

  2. 实时监测：ctDNA的半衰期短于2小时，能够更准确地反映患者的肿瘤负担，提供早期复发的预测。

  3. 个体化治疗：ctDNA分析能够动态监测肿瘤基因突变，帮助制定个性化的治疗方案。

主要结论/意义/创新性 ​

ctDNA作为液体活检的应用可能会引发肿瘤管理的革命。其在肿瘤的早期检测、治疗监测和预后评估中显示出巨大的潜力，为个体化医学的发展提供了新的方向。尽管ctDNA分析在临床应用中仍面临一些挑战，但随着技术的进步，其在常规临床实践中的应用前景乐观。

研究局限性和未来方向 ​

  1. 局限性：目前ctDNA的检测灵敏度仍需提高，特别是在早期癌症患者中。此外，样本量的限制和对特定突变的先验知识需求也限制了其应用。

  2. 未来方向：需要深入研究ctDNA的生物学特性及其释放机制，进一步验证ctDNA在临床中的分析有效性和临床效用，以推动其在常规临床实践中的应用。随着测序技术的快速发展，ctDNA的临床应用有望得到广泛推广。

参考文献 ​

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引用本文的文献 ​

  1. Integrating precision cancer medicine into healthcare-policy, practice, and research challenges. - Gabrielle Bertier;Jian Carrot-Zhang;Vassilis Ragoussis;Yann Joly - Genome medicine (2016)
  2. Liquid biopsy based biomarkers in non-small cell lung cancer for diagnosis and treatment monitoring. - David Pérez-Callejo;Atocha Romero;Mariano Provencio;María Torrente - Translational lung cancer research (2016)
  3. Diagnostic and prognostic value of circulating tumor DNA in gastric cancer: a meta-analysis. - Yunhe Gao;Kecheng Zhang;Hongqing Xi;Aizhen Cai;Xiaosong Wu;Jianxin Cui;Jiyang Li;Zhi Qiao;Bo Wei;Lin Chen - Oncotarget (2017)
  4. Liquid biopsies in bladder cancer-did we find the Holy Grail for biomarker analyses? - Michael Rink;Shahrokh F Shariat;Armin Soave - Translational andrology and urology (2016)
  5. Circulating Cell Free Tumor DNA Detection as a Routine Tool forLung Cancer Patient Management. - Julie A Vendrell;Frédéric Tran Mau-Them;Benoît Béganton;Sylvain Godreuil;Peter Coopman;Jérôme Solassol - International journal of molecular sciences (2017)
  6. Analysis of DNA Methylation Status in Bodily Fluids for Early Detection of Cancer. - Keigo Yokoi;Keishi Yamashita;Masahiko Watanabe - International journal of molecular sciences (2017)
  7. Circulating Tumor DNA as Biomarkers for Cancer Detection. - Xiao Han;Junyun Wang;Yingli Sun - Genomics, proteomics & bioinformatics (2017)
  8. Liquid biopsy: a step forward towards precision medicine in urologic malignancies. - Ashley Di Meo;Jenni Bartlett;Yufeng Cheng;Maria D Pasic;George M Yousef - Molecular cancer (2017)
  9. Pattern recognition for predictive, preventive, and personalized medicine in cancer. - Tingting Cheng;Xianquan Zhan - The EPMA journal (2017)
  10. The Role of BEAMing and Digital PCR for Multiplexed Analysis in Molecular Oncology in the Era of Next-Generation Sequencing. - Jérôme Alexandre Denis;Erell Guillerm;Florence Coulet;Annette K Larsen;Jean-Marc Lacorte - Molecular diagnosis & therapy (2017)

... (187 更多 篇文献)

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