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肝细胞癌中的液体活检:挑战、进展及临床意义

Liquid biopsy in hepatocellular carcinoma: Challenges, advances, and clinical implications.

作者信息

Park Jaeho, Lee Yi-Te, Agopian Vatche G, Liu Jessica S, Koltsova Ekaterina K, You Sungyong, Zhu Yazhen, Tseng Hsian-Rong, Yang Ju Dong

机构信息

Karsh Division of Gastroenterology and Hepatology, Cedars-Sinai Medical Center, Los Angeles, CA, USA.

Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA.

出版信息

Clin Mol Hepatol. 2025 Feb;31(Suppl):S255-S284. doi: 10.3350/cmh.2024.0541. Epub 2024 Nov 28.

DOI:10.3350/cmh.2024.0541
PMID:39604328
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11925447/
Abstract

Hepatocellular carcinoma (HCC) is an aggressive primary liver malignancy often diagnosed at an advanced stage, resulting in a poor prognosis. Accurate risk stratification and early detection of HCC are critical unmet needs for improving outcomes. Several blood-based biomarkers and imaging tests are available for early detection, prediction, and monitoring of HCC. However, serum protein biomarkers such as alpha-fetoprotein have shown relatively low sensitivity, leading to inaccurate performance. Imaging studies also face limitations related to suboptimal accuracy, high cost, and limited implementation. Recently, liquid biopsy techniques have gained attention for addressing these unmet needs. Liquid biopsy is non-invasive and provides more objective readouts, requiring less reliance on healthcare professional's skills compared to imaging. Circulating tumor cells, cell-free DNA, and extracellular vesicles are targeted in liquid biopsies as novel biomarkers for HCC. Despite their potential, there are debates regarding the role of these novel biomarkers in the HCC care continuum. This review article aims to discuss the technical challenges, recent technical advancements, advantages and disadvantages of these liquid biopsies, as well as their current clinical application and future directions of liquid biopsy in HCC.

摘要

肝细胞癌(HCC)是一种侵袭性原发性肝脏恶性肿瘤,通常在晚期才被诊断出来,预后较差。准确的风险分层和HCC的早期检测是改善治疗结果的关键未满足需求。有几种基于血液的生物标志物和影像学检查可用于HCC的早期检测、预测和监测。然而,血清蛋白生物标志物如甲胎蛋白的敏感性相对较低,导致检测结果不准确。影像学研究也面临着准确性欠佳、成本高和应用受限等问题。近年来,液体活检技术因满足这些未满足的需求而受到关注。液体活检是非侵入性的,能提供更客观的检测结果,与影像学相比,对医疗专业人员技能的依赖更少。循环肿瘤细胞、游离DNA和细胞外囊泡是液体活检中作为HCC新型生物标志物的检测目标。尽管它们具有潜力,但关于这些新型生物标志物在HCC治疗连续过程中的作用仍存在争议。这篇综述文章旨在讨论这些液体活检的技术挑战、最新技术进展、优缺点,以及它们在HCC中的当前临床应用和未来发展方向。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d940/11925447/3f86be6b903e/cmh-2024-0541f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d940/11925447/edcc72058b05/cmh-2024-0541f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d940/11925447/3f86be6b903e/cmh-2024-0541f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d940/11925447/edcc72058b05/cmh-2024-0541f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d940/11925447/3f86be6b903e/cmh-2024-0541f2.jpg

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本文引用的文献

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Extracellular vesicles in the HCC microenvironment: Implications for therapy and biomarkers.细胞外囊泡在 HCC 微环境中的作用:治疗和生物标志物的启示。
Pharmacol Res. 2024 Nov;209:107419. doi: 10.1016/j.phrs.2024.107419. Epub 2024 Sep 14.
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macrophages support fibroblasts in shaping tumor barrier and inducing poor clinical outcomes in liver cancer.巨噬细胞支持成纤维细胞塑造肿瘤屏障,并导致肝癌预后不良。
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Programmed Death Ligand 1 Expression in Circulating Tumor Cells as a Predictor and Monitor of Response to Atezolizumab plus Bevacizumab Treatment in Patients with Hepatocellular Carcinoma.程序性死亡配体1在循环肿瘤细胞中的表达作为肝细胞癌患者接受阿替利珠单抗联合贝伐单抗治疗反应的预测指标和监测指标
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Alpha-fetoprotein: Past, present, and future.甲胎蛋白:过去、现在与未来。
Hepatol Commun. 2024 Apr 12;8(5). doi: 10.1097/HC9.0000000000000422. eCollection 2024 May 1.
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Extracellular vesicles and cancer stemness in hepatocellular carcinoma - is there a link?细胞外囊泡与肝癌的肿瘤干性——它们之间是否存在关联?
Front Immunol. 2024 Feb 27;15:1368898. doi: 10.3389/fimmu.2024.1368898. eCollection 2024.
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Sci Rep. 2024 Mar 4;14(1):5322. doi: 10.1038/s41598-024-55888-8.
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