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Liquid biopsy in hepatocellular carcinoma: circulating tumor cells and circulating tumor DNA.

文献信息

DOI10.1186/s12943-019-1043-x
PMID31269959
期刊Molecular cancer
影响因子33.9
JCR 分区Q1
发表年份2019
被引次数202
关键词循环肿瘤DNA, 循环肿瘤细胞(CTCs), 临床应用, 肝细胞癌, 液体活检
文献类型Journal Article, Research Support, Non-U.S. Gov't, Review
ISSN1476-4598
页码114
期号18(1)
作者Qianwei Ye, Sunbin Ling, Shusen Zheng, Xiao Xu

一句话小结

肝细胞癌(HCC)是全球主要的癌症和死亡原因,传统的组织活检存在侵入性和样本不足的问题,急需新的诊断策略。本文综述了液体活检在HCC中的应用,重点讨论了循环肿瘤细胞(CTCs)和循环肿瘤DNA(ctDNA)的检测,这为早期诊断和监测肿瘤复发提供了无创且有效的手段。

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循环肿瘤DNA · 循环肿瘤细胞(CTCs) · 临床应用 · 肝细胞癌 · 液体活检

摘要

肝细胞癌(HCC)是最常见的癌症之一,也是全球主要死亡原因之一。由于潜在的肝病、晚期诊断以及对系统性治疗的无反应,外科切除和/或活检标本至今仍被临床医生普遍视为临床决策的金标准。由于传统的组织活检具有侵入性且样本量小,无法代表肿瘤的异质性或监测肿瘤动态进展。因此,迫切需要寻找一种新的、侵入性小或无创的诊断策略,以便在早期阶段检测HCC并监测HCC复发。近年来,一种被称为“液体活检”的新诊断概念引起了广泛关注。液体活检是无创的,允许重复分析以实时监测肿瘤复发、转移或治疗反应。随着新分子技术的不断发展,HCC循环肿瘤细胞(CTCs)和循环肿瘤DNA(ctDNA)的检测取得了令人兴奋和鼓舞人心的成果。在本综述中,我们重点讨论CTCs和ctDNA在HCC患者中作为液体活检关键组成部分的临床应用。

英文摘要

Hepatocellular carcinoma (HCC) is one of the most common cancers and a leading cause of death worldwide. Due to latent liver disease, late diagnosis, and nonresponse to systemic treatments, surgical resection and/or biopsy specimens are still generally considered as the gold standard by clinicians for clinical decision-making until now. Since the conventional tissue biopsy is invasive and contains small tissue samples, it is unable to represent tumor heterogeneity or monitor dynamic tumor progression. Therefore, it is imperative to find a new less invasive or noninvasive diagnostic strategy to detect HCC at an early stage and to monitor HCC recurrence. Over the past years, a new diagnostic concept known as "liquid biopsy" has emerged with substantial attention. Liquid biopsy is noninvasive and allows repeated analyses to monitor tumor recurrence, metastasis or treatment responses in real time. With the advanced development of new molecular techniques, HCC circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) detection have achieved interesting and encouraging results. In this review, we focus on the clinical applications of CTCs and ctDNA as key components of liquid biopsy in HCC patients.

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主要研究问题

  1. 液体活检在肝细胞癌的早期诊断中相较于传统组织活检有哪些具体优势?
  2. 在液体活检中,循环肿瘤细胞和循环肿瘤DNA的检测方法有哪些不同,如何选择使用?
  3. 如何评估液体活检在监测肝细胞癌复发和治疗反应中的有效性和准确性?
  4. 当前液体活检技术在肝细胞癌的临床应用中面临哪些挑战和局限性?
  5. 未来液体活检技术在肝细胞癌的研究和治疗中可能会有哪些新进展和应用方向?

核心洞察

研究背景和目的

肝细胞癌(HCC)是全球最常见的癌症之一,也是导致死亡的主要原因。由于晚期诊断和对系统性治疗的反应不足,外科切除和活检仍被认为是临床决策的金标准。然而,传统的组织活检具有侵入性,且样本量小,无法全面反映肿瘤的异质性和动态进展。因此,寻找一种新的、非侵入性的早期诊断策略以检测HCC及监测其复发显得尤为重要。本研究旨在探讨循环肿瘤细胞(CTCs)和循环肿瘤DNA(ctDNA)作为液体活检在HCC患者中的临床应用。

主要方法/材料/实验设计

液体活检的主要组成部分是CTCs和ctDNA。CTCs是从原发或转移肿瘤自然脱落后进入血液循环的癌细胞,ctDNA则是由肿瘤细胞的凋亡和坏死释放到血液中的DNA片段。以下是研究的技术路线图:

Mermaid diagram

关键结果和发现

  1. CTCs:CTCs在血液中的浓度非常低,通常需要高灵敏度的检测技术。CTCs的存在与肿瘤的复发和转移相关,但其在早期癌症诊断中的应用受到限制。
  2. ctDNA:ctDNA显示出较高的诊断价值,尤其是在早期HCC的检测中。ctDNA的甲基化模式在HCC的发生中起到重要作用,特定的甲基化基因组合能够有效区分HCC患者与健康对照组。
  3. 临床应用:研究表明,ctDNA和CTCs的检测可以用于监测肿瘤负担、评估手术效果及预测复发风险。

主要结论/意义/创新性

液体活检作为一种非侵入性的方法,能够实时监测肿瘤的进展和复发,并为个体化治疗提供潜在的生物标志物。CTCs和ctDNA的检测有助于克服传统活检的局限性,为HCC的早期诊断和监测提供了新的思路。

研究局限性和未来方向

尽管液体活检显示出广泛的临床应用潜力,但仍面临许多挑战,包括CTCs和ctDNA的生物学基础尚不明确,且目前的检测技术缺乏标准化。此外,未来需要进行多中心、大规模和长期的研究,以验证液体活检在临床实践中的有效性和可靠性。研究人员还应关注ctDNA的组织特异性和表观遗传标记的开发,以进一步提升液体活检的诊断能力。

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  2. The Role Of Circulating Tumor DNA In Therapeutic Resistance. - Chenxin Xu;Haixia Cao;Chen Shi;Jifeng Feng - OncoTargets and therapy (2019)
  3. Using circulating tumor DNA as a novel biomarker to screen and diagnose hepatocellular carcinoma: A systematic review and meta-analysis. - Ziying Zhang;Peng Chen;Hui Xie;Peiguo Cao - Cancer medicine (2020)
  4. Circulating tumor cells in cancer patients: developments and clinical applications for immunotherapy. - Xiaoming Zhong;Hangtian Zhang;Ying Zhu;Yuqing Liang;Zhuolin Yuan;Jiachen Li;Jing Li;Xin Li;Yifan Jia;Tian He;Jiangyuan Zhu;Yu Sun;Wengting Jiang;Hui Zhang;Cheng Wang;Zunfu Ke - Molecular cancer (2020)
  5. Detection of Circulating Tumor Cells and Their Implications as a Biomarker for Diagnosis, Prognostication, and Therapeutic Monitoring in Hepatocellular Carcinoma. - Joseph C Ahn;Pai-Chi Teng;Pin-Jung Chen;Edwin Posadas;Hsian-Rong Tseng;Shelly C Lu;Ju Dong Yang - Hepatology (Baltimore, Md.) (2021)
  6. Sequential Circulating Tumor Cell Counts in Patients with Locally Advanced or Metastatic Hepatocellular Carcinoma: Monitoring the Treatment Response. - Kun-Ming Rau;Chien-Ting Liu;Yu-Chiao Hsiao;Kai-Yin Hsiao;Tzu-Min Wang;Wei-Shan Hung;Yu-Li Su;Wei-Ching Liu;Cheng-Hsu Wang;Hsueh-Ling Hsu;Po-Heng Chuang;Ju-Chien Cheng;Ching-Ping Tseng - Journal of clinical medicine (2020)
  7. Novel Liquid Biopsy Test Based on a Sensitive Methylated SEPT9 Assay for Diagnosing Hepatocellular Carcinoma. - Yurika Kotoh;Yutaka Suehiro;Issei Saeki;Tomomi Hoshida;Masaki Maeda;Takuya Iwamoto;Toshihiko Matsumoto;Isao Hidaka;Tsuyoshi Ishikawa;Taro Takami;Shingo Higaki;Ikuei Fujii;Chieko Suzuki;Yoshitaro Shindo;Yukio Tokumitsu;Hiroaki Nagano;Isao Sakaida;Takahiro Yamasaki - Hepatology communications (2020)
  8. LncRNA FLJ33360 accelerates the metastasis in hepatocellular carcinoma by targeting miRNA-140/MMP9 axis. - Zhenhui Lu;Yingzi Yu;Xiangchun Ding;Dong Jin;Genwang Wang;Yu Zhou;Yongzhao Zhu;Li Na;Yaqin He;Qi Wang - American journal of translational research (2020)
  9. Emerging and Innovative Theranostic Approaches for Mesoporous Silica Nanoparticles in Hepatocellular Carcinoma: Current Status and Advances. - Yaoye Tao;Jianguo Wang;Xiao Xu - Frontiers in bioengineering and biotechnology (2020)
  10. Impact of Next-Generation Sequencing on Outcomes in Hepatocellular Carcinoma: How Precise Are We Really? - Dana A Dominguez;Xin Wei Wang - Journal of hepatocellular carcinoma (2020)

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