Detection of Circulating Tumor Cells and Their Implications as a Biomarker for Diagnosis, Prognostication, and Therapeutic Monitoring in Hepatocellular Carcinoma

Abstract

Hepatocellular carcinoma (HCC) is among the leading causes of worldwide cancer‐related morbidity and mortality. Poor prognosis of HCC is attributed primarily to tumor presentation at an advanced stage when there is no effective treatment to achieve the long term survival of patients. Currently available tests such as alpha‐fetoprotein have limited accuracy as a diagnostic or prognostic biomarker for HCC. Liver biopsy provides tissue that can reveal tumor biology but it is not used routinely due to its invasiveness and risk of tumor seeding, especially in early‐stage patients. Liver biopsy is also limited in revealing comprehensive tumor biology due to intratumoral heterogeneity. There is a clear need for new biomarkers to improve HCC detection, prognostication, prediction of treatment response, and disease monitoring with treatment. Liquid biopsy could be an effective method of early detection and management of HCC. Circulating tumor cells (CTCs) are cancer cells in circulation derived from the original tumor or metastatic foci, and their measurement by liquid biopsy represents a great potential in facilitating the implementation of precision medicine in patients with HCC. CTCs can be detected by a simple peripheral blood draw and potentially show global features of tumor characteristics. Various CTC detection platforms using immunoaffinity and biophysical properties have been developed to identify and capture CTCs with high efficiency. Quantitative abundance of CTCs, as well as biological characteristics and genomic heterogeneity among the CTCs, can predict disease prognosis and response to therapy in patients with HCC. This review article will discuss the currently available technologies for CTC detection and isolation, their utility in the clinical management of HCC patients, their limitations, and future directions of research.

Detection of circulating tumor cells in hepatocellular carcinoma: applications in diagnosis, prognosis prediction and personalized treatment

“…CTCs have shown great potential for the early diagnosis and prognostication of HCC patients [14] . The clinical applications of CTC detection in patients with HCC are summarized in Table 2.…”

“…Surgical resection remains the most effective therapy for HCC. CTCs could serve as a complementary tool to assess the efficacy of surgical resection and monitor tumor progression [8,14] . Qi et al [98] recently compared the outcomes of patients undergoing anatomical or non-anatomical resection according to the number and EMT phenotype of CTCs.…”

“…CTCs represent a unique liquid biopsy form that is different from any of the existing cancer biomarkers, as they are a sampling of the patient's live tumor cells, carrying comprehensive biological information of the primary tumor, including genomic mutations, cancer subtypes, and drug sensitivity [12] . CTC research has flourished over the past decade, spanning fields including CTC detection, identification of prognostic significance, and evaluation for treatment response and disease surveillance [13,14] .…”

“…In the context of HCC, excellent progress has been made using CTCs as blood-based biomarkers [9,14,15] . Herein, to gain comprehensive insight into the role of CTCs in HCC, this review article provides an overview of their biology, detection technologies, and clinical significance in HCC.…”

Preoperative circulating tumor cells to predict microvascular invasion and dynamical detection indicate the prognosis of hepatocellular carcinoma

“…In addition, several CTCs aggregate to form CTC clusters, which have a signi cantly greater potential to play an important role in cancer metastasis than single CTCs [14]. The liquid biopsy technique represented by CTC detection has great potential to contribute to the implementation of precision medicine in patients with HCC [15]. CTCs obtained by the liquid biopsy technique can be used to evaluate the presence of MVI.…”