To clarify the significance of circulating tumor cells (CTC) undergoing epithelial-mesenchymal transition (EMT) in patients with hepatocellular carcinoma (HCC), we used an advanced CanPatrol CTC-enrichment technique and hybridization to enrich and classify CTC from blood samples. One hundred and one of 112 (90.18%) patients with HCC were CTC positive, even with early-stage disease. CTCs were also detected in 2 of 12 patients with hepatitis B virus (HBV), both of whom had small HCC tumors detected within 5 months. CTC count ≥16 and mesenchymal-CTC (M-CTC) percentage ≥2% prior to resection were significantly associated with early recurrence, multi-intrahepatic recurrence, and lung metastasis. Postoperative CTC monitoring in 10 patients found that most had an increased CTC count and M-CTC percentage before clinically detectable recurrence nodules appeared. Analysis of HCC with high CTC count and high M-CTC percentage identified 67 differentially expressed cancer-related genes involved in cancer-related biological pathways (e.g., cell adhesion and migration, tumor angiogenesis, and apoptosis). One of the identified genes, BCAT1, was significantly upregulated, and knockdown in Hepg2, Hep3B, and Huh7 cells reduced cell proliferation, migration, and invasion while promoting apoptosis. A concomitant increase in epithelial marker expression (EpCAM and E-cadherin) and reduced mesenchymal marker expression (vimentin and Twist) suggest that BCAT1 may trigger the EMT process. Overall, CTCs were highly correlated with HCC characteristics, representing a novel marker for early diagnosis and a prognostic factor for early recurrence. BCAT1 overexpression may induce CTC release by triggering EMT and may be an important biomarker of HCC metastasis. In liver cancer, CTC examination may represent an important "liquid biopsy" tool to detect both early disease and recurrent or metastatic disease, providing cues for early intervention or adjuvant therapy. .

Molecular targeted therapy for advanced hepatocellular carcinoma (HCC) has changed markedly. Although sorafenib was used in clinical practice as the first molecular targeted agent in 2007, the SHARPE and Asian-Pacific trials demonstrated that sorafenib only improved overall survival (OS) by approximately 3 months in patients with advanced HCC compared with placebo. Molecular targeted agents were developed during the 10-year period from 2007 to 2016, but every test of these agents from phase II or phase III clinical trial failed due to a low response rate and high toxicity. In the 2 years after, 2017 through 2018, four successful novel drugs emerged from clinical trials for clinical use. As recommended by updated Barcelona Clinical Liver cancer (BCLC) treatment algorithms, lenvatinib is now feasible as an alternative to sorafenib as a first-line treatment for advanced HCC. Regorafenib, cabozantinib, and ramucirumab are appropriate supplements for sorafenib as second-line treatment for patients with advanced HCC who are resistant, show progression or do not tolerate sorafenib. In addition, with promising outcomes in phase II trials, immune PD-1/PD-L1 checkpoint inhibitors nivolumab and pembrolizumab have been applied for HCC treatment. Despite phase III trials for nivolumab and pembrolizumab, the primary endpoints of improved OS were not statistically significant, immune PD-1/PD-L1 checkpoint therapy remains to be further investigated. This review summarizes the development and progression of molecular targeted and immune-based checkpoint therapies in HCC.

As a pleiotropic cytokine, interleukin-6 (IL-6) not only regulates the cellular immune response, but it also promotes tumor development by activating multiple carcinogenic pathways. IL-6 expression is significantly elevated in colorectal cancer (CRC) and is closely related to CRC development and patient prognosis. In CRC, IL-6 activates signal transducers and activators of transduction-3 (STAT3) to promote tumor initiation and tumor growth. IL-6/STAT3 signalling has a profound effect on tumor-infiltrating immune cells in the tumor immune microenvironment in CRC. Additionally, IL-6/STAT3 pathway activates downstream target genes to protect tumor cells from apoptosis; drive tumor cell proliferation, cell cycle progression, invasion and metastasis; promote tumor angiogenesis; and stimulate drug resistance. Therefore, a thorough understanding of the many effects of the IL-6/STAT3 pathway in CRC is needed, which the present review examines.

Surgical resection is the most effective therapeutic strategy for HCC patients with PVTT and results in high hepatic functional reserve. For patients who can tolerate the procedure, postoperative TACE is necessary to prevent recurrence and prolong the survival period.

AIMTo investigate the efficacy and safety of postoperative adjuvant transcatheter arterial chemoembolization (PA-TACE) in preventing tumor recurrence and improving survival in Barcelona Clinic Liver Cancer (BCLC) early (A) and intermediate (B) stage hepatocellular carcinoma (HCC) patients with microvascular invasion (MVI).METHODSA total of 519 BCLC A or B HCC patients treated by liver resection alone or followed by PA-TACE between January 2012 and December 2015 were studied retrospectively. Univariate and multivariate analyses were performed to investigate the risk factors for recurrence-free survival (RFS) and overall survival (OS). Multiple logistic regression was used to identify the clinicopathological characteristics associated with MVI. The rates of RFS and OS were compared among patients with or without MVI treated with liver resection alone or followed by PA-TACE.RESULTSUnivariate and multivariate analyses demonstrated that serum AFP level > 400 ng/mL, tumor size > 5 cm, tumor capsule invasion, MVI, and major hepatectomy were risk factors for poor OS. Tumor capsule invasion, MVI, tumor size > 5 cm, HBV-DNA copies > 1 x 104 IU/mL, and multinodularity were risk factors for poor RFS. Multiple logistic regression identified serum AFP level > 400 ng/mL, tumor size > 5 cm, and tumor capsule invasion as independent predictors of MVI. Both OS and DFS were significantly improved in patients with MVI who received PA-TACE as compared to those who underwent liver resection alone. Patients without MVI did not show a significant difference in OS and RFS between those treated by liver resection alone or followed by PA-TACE.CONCLUSIONPA-TACE is a safe adjuvant intervention and can efficiently prevent tumor recurrence and improve the survival of BCLC early- and intermediate-stage HCC patients with MVI.