Clinical Implication of Circulating Tumor Cells Expressing Epithelial Mesenchymal Transition (EMT) and Cancer Stem Cell (CSC) Markers and Their Perspective in HCC: A Systematic Review

Abstract

Circulating tumor cells (CTCs) play a key role in hematogenous metastasis and post-surgery recurrence. In hepatocellular carcinoma (HCC), CTCs have emerged as a valuable source of therapeutically relevant information. Certain subsets or phenotypes of CTCs can survive in the bloodstream and induce metastasis. Here, we performed a systematic review on the importance of epithelial–mesenchymal transition (EMT)-CTCs and circulating cancer stem cells (CCSCs) in metastatic processes and their prognostic power in HCC management. PubMed, Scopus, and Embase databases were searched for relevant publications. PRISMA criteria were used to review all studies. Twenty publications were eligible, of which 14, 5, and 1 study reported EMT-CTCs, CCSCs, and both phenotypes, respectively. Most studies evaluated that mesenchymal CTCs and CCSCs positivity were statistically associated with extensive clinicopathological features, including larger size and multiple numbers of tumors, advanced stages, micro/macrovascular invasion, and metastatic/recurrent disease. A preliminary meta-analysis showed that the presence of mesenchymal CTCs in pre- and postoperative blood significantly increased the risk of early recurrence. Mesenchymal-CTCs positivity was the most reported association with inferior outcomes based on the prognosis of HCC recurrence. Our finding could be a step forward, conveying additional prognostic values of CTC subtypes as promising biomarkers in HCC management.

Stromal interaction molecule 1/microtubule‐associated protein 1A/1B‐light chain 3B complex induces metastasis of hepatocellular carcinoma by promoting autophagy

“…Abundant evidence suggests that autophagy facilitates EMT and tumor metastasis in the late stages of tumor development 5,6 . In this study, we report that STIM1 is temporally regulated during autophagy‐triggered EMT in HCC cells.…”

“…Abundant evidence suggests that autophagy facilitates EMT and tumor metastasis in the late stages of tumor development. 5,6 In this study, we report that STIM1 is temporally regulated during autophagy-triggered EMT in HCC cells. Furthermore, we demonstrate that STIM1 promotes autophagy through both SOCE-dependent and SOCE-independent mechanisms.…”

“…Accumulating evidence suggests that autophagy plays a crucial role in EMT process, making it a potential target for preventing HCC metastasis. 5,6 Autophagy, an important self-protective mechanism of cancer cells, regulates the orderly degradation and recycling of cellular components. 7 This process involves sequestering waste products into autophagosomes, which are then degraded by lysosomes.…”

Analysis of Preoperative Risk Factors for Early Recurrence in Patients After Hepatic Resection for Intrahepatic Cholangiocarcinoma

“…12 In the present study, tumor size, together with CAR, was an independent predictor of early recurrence after surgery. Since larger tumors have been associated with a higher positive rate of circulating cancer cells in the blood, 13 patients with larger tumors may more frequently develop early recurrences after surgery. Systemic inflammation can accelerate cancer metastasis by promoting the binding of circulating tumor cells to the vascular endothelium.…”

Molecular mechanism of WWP1‐mediated ubiquitination modification affecting proliferation and invasion/migration of liver cancer cells

“…Moreover, epithelial‐to‐mesenchymal transition (EMT) is a multi‐step biological process in which epithelial tumor cells lose their adhesion capacities due to the downregulation of epithelial cell adhesion molecules. These cells then acquire mesenchymal features that promote cancer cell motility and invasiveness 39 . Therefore, the phenotypic hallmarks of EMT are important paradigms of HCC metastasis.…”