Clinical applications of circulating tumor cells in hepatocellular carcinoma

Abstract

Hepatocellular carcinoma (HCC) is a highly malignant tumor and ranked as the fourth cause of cancer-related mortality. The poor clinical prognosis is due to an advanced stage and resistance to systemic treatment. There are no obvious clinical symptoms in the early stage and the early diagnosis rate remains low. Novel effective biomarkers are important for early diagnosis and tumor surveillance to improve the survival of HCC patients. Circulating tumor cells (CTCs) are cancer cells shed from primary or metastatic tumor and extravasate into the blood system. The number of CTCs is closely related to the metastasis of various solid tumors. CTCs escape from blood vessels and settle in target organs, then form micro-metastasis. Epithelial-mesenchymal transformation (EMT) plays a crucial role in distant metastasis, which confers strong invasiveness to CTCs. The fact that CTCs can provide complete cellular biological information, which allows CTCs to be one of the most promising liquid biopsy targets. Recent studies have shown that CTCs are good candidates for early diagnosis, prognosis evaluation of metastasis or recurrence, and even a potential therapeutic target in patients with HCC. It is a new indicator for clinical application in the future. In this review, we introduce the enrichment methods and mechanisms of CTCs, and focus on clinical application in patients with HCC.

Mechanisms of portal vein tumour thrombus formation and development in patients with hepatocellular carcinoma

“…Moreover, CTCs are considered to be an active source of metastases due to their potential stem cell features and EMT traits, which allow them to disseminate effectively. From the perspective of tumour microenvironment, the generation of CTC is a part of the transformation of ECM and EMT 90 . Researchers have noticed that CTCs obtained mesenchymal features via EMT, and then infiltrated the ECM by releasing proteolytic degradation enzymes and crossing the basement membrane.…”

“…Intense correlation of HIF-1α signalling pathways and PVTT 59,60 Features StemcellandEMTtraits 90 Molecularmechanisms Hypoxia/14-3-3ζ/HIF-1α/EMTpathway, 19 Hypoxia/HIF-1α /CCL20/IDO axis 20…”

“…From the perspective of tumour microenvironment, the generation of CTC is a part of the transformation of ECM and EMT. 90 Researchers have noticed that CTCs obtained mesenchymal features via EMT, and then infiltrated the ECM by releasing proteolytic degradation enzymes and crossing the basement membrane. Eventually, they passed into the circulation and extravasated to form secondary micro‐metastasis.…”

Liquid Biopsy in Hepatocellular Carcinoma: The Significance of Circulating Tumor Cells in Diagnosis, Prognosis, and Treatment Monitoring

“…About 40% of the HCCs do not exhibit elevated AFP levels [ 16 ]. Combining US with AFP testing can improve the sensitivity of early detection from 45% to 63% [ 17 ]. Although abdominal US is highly accurate (sensitivity: 58–89%, specificity: >90%), its ability to detect small or early-stage nodules is limited [ 17 , 18 ].…”

“…Combining US with AFP testing can improve the sensitivity of early detection from 45% to 63% [ 17 ]. Although abdominal US is highly accurate (sensitivity: 58–89%, specificity: >90%), its ability to detect small or early-stage nodules is limited [ 17 , 18 ]. Advanced imaging techniques, such as computed tomography (CT) or magnetic resonance imaging (MRI) with new contrast agents, have revolutionized the diagnosis of early-stage HCC.…”