Utility of Liquid Biopsy Analysis in Detection of Hepatocellular Carcinoma, Determination of Prognosis, and Disease Monitoring: A Systematic Review.
Utility of Liquid Biopsy Analysis in Detection of Hepatocellular Carcinoma, Determination of Prognosis, and Disease Monitoring: A Systematic Review.
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DOI：
10.1016/j.cgh.2020.04.019
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发表时间：
2020-12
期刊：
影响因子：
--
通讯作者：
Parikh ND
中科院分区：
文献类型：
--
作者：
Chen VL;Xu D;Wicha MS;Lok AS;Parikh ND
可以分析液体活检或血液样本来检测循环肿瘤细胞 (CTC)、游离 DNA (cfDNA) 和细胞外囊泡，这可能会识别肝细胞癌 (HCC) 患者或帮助确定他们的预后。我们对 HCC 患者液体活检分析及其与其他生物标志物的比较进行了系统回顾。我们对 2019 年 12 月 1 日之前发表的原始研究进行了系统回顾。我们纳入了单独比较液体活检以及与其他生物标志物联合检测 HCC 的研究，对液体活检分析在确定患者预后方面的准确性进行了多变量分析，或评估了液体活检分析在监测治疗反应中的效用。我们的最终分析包括 112 项研究：67 项关于检测，46 项关于确定预后，25 项关于治疗监测或选择。十项研究评估了将 cfDNA 与甲胎蛋白 (AFP) 测量相结合来检测 HCC 的分析方法，这些研究发现，cfDNA 和 AFP 的联合测量比单独测量 AFP 更能准确地识别 HCC 患者。六项研究评估了细胞外囊泡的检测，两项研究评估了 CTC 检测在 HCC 检测中的检测（无论有或没有其他生物标志物）——大多数研究发现，与单独测量 AFP 相比，用 AFP 检测 CTC 或细胞外囊泡可以更准确地识别 HCC 患者。在 14 项研究中，有 13 项研究显示手术前 CTC 检测与切除后 HCC 复发相关； cfDNA 和细胞外囊泡作为预后因素的研究较少。治疗前后 CTC 数量的变化比单独治疗前的计数更能准确地识别 HCC 复发患者，并且 cfDNA 测量可以在通过影像学检测变化之前识别疾病复发或进展的患者。我们发现几乎没有证据表明液体活检分析可以帮助选择 HCC 治疗方法。质量评估显示 HCC 检测和预后确定研究存在偏倚风险。在对 112 项液体活检分析准确性的研究进行系统评价时，我们发现 CTC 和 cfDNA 检测可能有助于确定患者预后和监测 HCC，而 cfDNA 检测可能有助于 HCC 检测，但这些研究存在偏倚风险。在我们评估液体活检分析在 HCC 患者检测和管理中的临床效用之前，必须对研究进行标准化。
Liquid biopsies, or blood samples, can be analyzed to detect circulating tumor cells (CTCs), cell-free DNA (cfDNA), and extracellular vesicles, which might identify patients with hepatocellular carcinoma (HCC) or help determine their prognoses. We performed a systematic review of studies of analyses of liquid biopsies from patients with HCC and their comparisons with other biomarkers. We performed a systematic review of original studies published before December 1, 2019. We included studies that compared liquid biopsies alone and in combination with other biomarkers for the detection of HCC, performed multivariate analyses of the accuracy of liquid biopsy analysis in determining patient prognoses, or evaluated the utility of liquid biopsy analysis in monitoring treatment response. Our final analysis included 112 studies: 67 on detection, 46 on determining prognosis, and 25 on treatment monitoring or selection. Ten studies evaluated assays that characterized cfDNA for detection of HCC in combination with measurement of α-fetoprotein (AFP)—these studies found that the combined measurement of cfDNA and AFP more accurately identified patients with HCC than measurement of AFP alone. Six studies evaluated assays for extracellular vesicles and 2 studies evaluated assays for CTC in detection of HCC, with and without other biomarkers—most of these studies found that detection of CTCs or extracellular vesicles with AFP more accurately identified patients with HCC than measurement of AFP alone. Detection of CTCs before surgery was associated with HCC recurrence after resection in 13 of 14 studies; cfDNA and extracellular vesicles have been studied less frequently as prognostic factors. Changes in CTC numbers before vs after treatment more accurately identify patients with HCC recurrence than pretreatment counts alone, and measurements of cfDNA can identify patients with disease recurrence or progression before changes can be detected by imaging. We found little evidence that analyses of liquid biopsies can aid in the selection of treatment for HCC. Quality assessment showed risk of bias in studies of HCC detection and determination of prognosis. In a systematic review of 112 studies of the accuracy of liquid biopsy analysis, we found that assays for CTCs and cfDNA might aid in determining patient prognoses and monitoring HCC, and assays for cfDNA might aid in HCC detection, but there is a risk of bias in these studies. Studies must be standardized before we can assess the clinical utility of liquid biopsy analysis in the detection and management of patients with HCC.
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