Department of Education and Research, Taipei City Hospital Renai Branch, Taipei, Taiwan.
Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA.
J Gastroenterol Hepatol. 2022 Jul;37(7):1179-1190. doi: 10.1111/jgh.15886. Epub 2022 May 16.
Serum alpha-fetoprotein and radiologic imaging are the most commonly used tests for early diagnosis and dynamic monitoring of treatment response in hepatocellular carcinoma (HCC). However, the accuracy of these tests is limited, and they may not reflect the underlying biology of the tumor. Thus, developing highly accurate novel HCC biomarkers reflecting tumor biology is a clinically unmet need. Circulating tumor cells (CTCs) have long been proposed as a noninvasive biomarker in clinical oncology. Most CTC assays utilize immunoaffinity-based, size-based, and/or enrichment-free mechanisms followed by immunocytochemical staining to characterize CTCs. The prognostic value of HCC CTC enumeration has been extensively validated. Subsets of CTCs expressing mesenchymal markers are also reported to have clinical significance. In addition, researchers have been devoting their efforts to molecular characterizations of CTCs (e.g. genetics and transcriptomics) as molecular profiling can offer a more accurate readout and provide biological insights. As new molecular profiling techniques, such as digital polymerase chain reaction, are developed to detect minimal amounts of DNA/RNA, several research groups have established HCC CTC digital scoring systems to quantify clinically relevant gene panels. Given the versatility of CTCs to provide intact molecular and functional data that reflects the underlying tumor, CTCs have great potential as a noninvasive biomarker in HCC. Large-scale, prospective studies for HCC CTCs with a standardized protocol are necessary for successful clinical translation.
血清甲胎蛋白和影像学检查是肝癌（HCC）早期诊断和治疗反应动态监测最常用的检测方法。然而，这些检测方法的准确性有限，并且可能无法反映肿瘤的基础生物学特性。因此，开发高度准确的新型 HCC 生物标志物反映肿瘤生物学特性是临床未满足的需求。循环肿瘤细胞（CTC）长期以来一直被提议作为临床肿瘤学的一种非侵入性生物标志物。大多数 CTC 检测方法利用免疫亲和、基于大小和/或无富集机制，然后进行免疫细胞化学染色来表征 CTC。HCC CTC 计数的预后价值已得到广泛验证。还报道了表达间充质标志物的 CTC 亚群具有临床意义。此外，研究人员一直在致力于 CTC 的分子特征（例如遗传学和转录组学），因为分子分析可以提供更准确的读数并提供生物学见解。随着用于检测微量 DNA/RNA 的新分子分析技术，如数字聚合酶链反应的发展，一些研究小组已经建立了 HCC CTC 数字评分系统来定量临床相关基因谱。鉴于 CTC 能够提供反映基础肿瘤的完整分子和功能数据的多功能性，CTC 作为 HCC 的非侵入性生物标志物具有很大的潜力。需要进行具有标准化方案的 HCC CTC 的大规模前瞻性研究，以实现成功的临床转化。
