The Significance of Circulating Tumor Cells in Patients with Hepatocellular Carcinoma: Real-Time Monitoring and Moving Targets for Cancer Therapy

Abstract

<jats:p>Hepatocellular carcinoma (HCC) is ranked as the sixth most common cancer around the world. With the emergence of the state-of-the-art modalities lately, such as liver transplantation, image-guided ablation, and chemoembolization, the death rate is still high due to high metastasis rate after therapy. Observation by biannual ultrasonography allows effective diagnosis at an early stage for candidates with no extrahepatic metastasis, but its effectiveness still remains unsatisfactory. Developing a new test with improved effectiveness and specificity is urgently needed for HCC diagnosis, especially for patients after first line therapy. Circulating tumor cells (CTCs) are a small sub-population of tumor cells in human peripheral blood, they release from the primary tumor and invade into the blood circulatory system, thereby residing into the distal tissues and survive. As CTCs have specific and aggressive properties, they can evade from immune defenses, induce gene alterations, and modulate signal transductions. Ultimately, CTCs can manipulate tumor behaviors and patient reactions to anti-tumor treatment. Given the fact that in HCC blood is present around the immediate vicinity of the tumor, which allows thousands of CTCs to release into the blood circulation daily, so CTCs are considered to be the main cause for HCC occurrence, and are also a pivotal factor for HCC prognosis. In this review, we highlight the characteristics and enrichment strategies of CTCs, and focus on the use of CTCs for tumor evaluation and management in patients with HCC.</jats:p>

Measurement of Circulating Tumor Cells Determines Treatment Response and Exitus in Patients with Hepatocellular Carcinoma Submitted to Transarterial Chemoembolization

“…Regarding CTCs counts, IsoFlux provided higher CTCs counts than CellSearch, with established cutoffs of no more than 5 CTCs for bad prognosis (27)(28)(29). In particular, the use of EMT markers for the identification of CTCs appeared to be especially appropriate for the measurement of CTCs in intermediate HCC stages, when activation of shedding of tumor cells into bloodstream widely occurs (30). 7).…”

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

“…The CellSearch TM system is the gold standard for capturing CTCs based on epithelial cell adhesion molecules (EpCAMs), which represent aggressive stem cell-like CTCs. [23,24]. However, a recent study showed that in the blood of a total of 14 HCC patients, the percentage of EpCAM-positive CTCs was only 8.03% [25].…”

Tumor Hypoxia and Circulating Tumor Cells

“…Just like the CSCs, circulating tumor stem-like cells also have different phenotypes depending on the primary tumor. A positive correlation among CD133+, level of Annexin A3 (ANXA3), and CTCs has been found for the Hepatocarcinoma CTCs [ 62 ].…”