Hepatocellular carcinoma: Mechanisms of progression and immunotherapy

Yu, Jian; Han, Qiuju; Zhang, Jian

doi:10.3748/wjg.v25.i25.3151

Cited by 98 publications

(71 citation statements)

References 166 publications

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“…Tumor proliferation and metastasis are significant hallmarks of HCC; hence, studies on these aspects would find therapeutic targets to control disease progression [39]. It is widely known that continuous activation of multiple pathways leads to uncontrolled cell proliferation and promotes tumor metastasis [40,41]. We found that PRELP knockdown promoted, while PRELP overexpression inhibited cell proliferation and migration.…”

Section: Discussionmentioning

confidence: 69%

PRELP has prognostic value and regulates cell proliferation and migration in hepatocellular carcinoma

Hong

Niu

et al. 2020

J. Cancer

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Purpose: Hepatocellular carcinoma (HCC) is an aggressive and prevalent tumor threatening human health. A previous study suggested low PRELP (proline/arginine-rich end leucine-rich repeat protein) expression was associated with poor patient survival in pancreatic ductal adenocarcinoma (PDAC). However, the role of PRELP in HCC has not yet been illuminated. Methods: PRELP expression analyses were carried out using transcriptomic datasets from the Integrative Molecular Database of Hepatocellular Carcinoma (HCCDB). The correlations between PRELP expression and clinicopathological features, and prognostic analyses were performed with a tissue microarray (TMA) and immunohistochemistry (IHC). The endogenous expression and in vitro roles of PRELP were investigated in cultured HCC cell lines. The potential mechanisms were characterized by a Gene Set Enrichment Analysis (GSEA) and gene-gene correlation analyses. Results: We found that PRELP mRNA expression was dramatically decreased in HCCs in comparison with that in adjacent normal tissues (NTs) or hepatic cirrhosis. IHC staining showed that PRELP was down-regulated in HCCs, which mainly located in cytoplasm, and was also found in nuclei. The correlation analyses revealed that PRELP expression was relevant to later p-stages (p= 0.028) and tumor size (p= 0.001). The overall survival (OS) and relapse free survival (RFS) time was shorter in HCC patients with lower PRELP expression levels than that with higher PRELP expression levels. Overexpression of PRELP inhibited, while knockdown of PRELP promoted proliferation and migration of HCC cells. For potential mechanisms, PRELP may inhibit progression of HCCs by interacting with integrin family members and the extracellular microenvironment. Conclusion: Our findings demonstrated that overexpression of PRELP correlates with better patient survival and inhibits both cell proliferation and migration in HCC. Therefore, PRELP can serve as a potential prognostic biomarker and therapeutic target which deserves further investigation.

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Section: Discussionmentioning

confidence: 69%

PRELP has prognostic value and regulates cell proliferation and migration in hepatocellular carcinoma

Hong

Niu

et al. 2020

J. Cancer

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“…Liver cancer always occurs in the context of chronic inflammation, which is an immunosuppressive environment mediated by hepatocytes (27,29). Under these inflammatory conditions, the inhibition of antigen-specific immune monitoring is partially mediated by changes in the molecular expression of immunosuppressive checkpoints and dendritic cell function, increasing regulatory T cell numbers and the release of immunosuppressive cytokines, such as interleukin-10 (IL-10) and transforming growth factor (TGF)-β (30)(31)(32). Long-term exposure to antigens can also lead to the overexpression of immunosuppressive checkpoint molecules on T cells, thus resulting in energy failure or cell exhaustion (26,31).…”

Section: Immune Recognition Tolerance and Escape Of Hccmentioning

confidence: 99%

“…Long-term exposure to antigens can also lead to the overexpression of immunosuppressive checkpoint molecules on T cells, thus resulting in energy failure or cell exhaustion (26,31). Meanwhile, HCC creates an immunosuppressive microenvironment through the expression of immunosuppressive factors that inhibit antigen presentation and the immune response, thus preventing an effective antitumor response and permitting further escape of immune surveillance (26,31). Through the abnormal expression of antigens, secretion of metabolites and cytokines and the change of the immune microenvironment, liver cancer cells can escape antitumor responses, resulting in immune escape of the tumor (33).…”

Section: Immune Recognition Tolerance and Escape Of Hccmentioning

confidence: 99%

Current progress and prospect of immune checkpoint inhibitors in hepatocellular carcinoma (Review)

2020

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In recent years, the incidence of liver cancer has increased and is currently the sixth most common tumor and the second leading cause of cancer-associated mortality worldwide. Most cases of liver cancer are hepatocellular carcinoma (HCC). Surgery, including liver transplantation or resection, and radiofrequency ablation therapies are all considered to be the curative treatment options for early-stage HCC. However, most patients have advanced HCC at the time of diagnosis, contributing to a poor prognosis. Therefore, improved treatment for late-stage HCC is needed. Immune checkpoint inhibitors (ICIs), among which programmed death receptor 1 (PD-1)/PD-ligand 1 and cytotoxic T lymphocyte-associated protein 4 are the representative immunological checkpoints, have shown great promise and progress for HCC treatment. The present review summarizes recent studies that have focused on ICIs and discusses the present limitations affecting the development of new therapeutic strategies.

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“…Hepatocellular carcinoma (HCC) is a common malignant tumor with characteristics of poor prognosis and high morbidity and mortality worldwide [1,2]. Various factors have been identified to contribute to the occurrence and progression of HCC, including the infection by hepatitis B or C virus, the inactivation of tumor suppressor genes such as p53, the abnormal activation of oncogenes such as K-ras and some signaling molecules such as PI3K, ERK/MAPK and Wnt/β-catenin as well as the evasion of the host immune system [3,4]. For the management of HCC, resection, liver transplantation and radiofrequency ablation are options for early-stage HCC patients, yet with high rates of recurrence and metastasis [3,5,6].…”

Section: Introductionmentioning

confidence: 99%

Acteoside as a potential therapeutic option for primary hepatocellular carcinoma: a preclinical study

Wang

Liu

et al. 2020

BMC Cancer

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Background Hepatocellular carcinoma (HCC) is a common malignant tumor with characteristics of poor prognosis, high morbidity and mortality worldwide. In particular, only a few systemic treatment options are available for advanced HCC patients, and include sorafenib and the recently described atezolizumab plus bevacizumab regimen as possible first-line treatments. We here propose acteoside, a phenylethanoid glycoside widely distributed in many medicinal plants as a potential candidate against advanced HCC. Methods Cell proliferation, colony formation and migration were analyzed in the three human HCC cell lines BEL7404, HLF and JHH-7. Angiogenesis assay was performed using HUVESs. The BEL7404 or JHH-7 xenograft nude mice model was established to analyze the possible antitumor effects of acteoside. qRT-PCR and western blotting were used to reveal the potential antitumor mechanisms of acteoside. Results Acteoside inhibited cell proliferation, colony formation and migration in all the three human HCC cell lines BEL7404, HLF and JHH-7. The prohibition of angiogenesis by acteoside was revealed by the inhibition of tube formation and cell migration of HUVECs. The combination of acteoside and sorafenib produced stronger inhibition of cell colony formation and migration of the HCC cells as well as of angiogenesis of HUVECs. The in vivo antitumor efficacy of acteoside was further demonstrated in BEL7404 or JHH-7 xenograft nude mice model, with an enhancement when combined with sorafenib in inhibiting the growth of JHH-7 xenograft. Further treatment of JHH-7 cells with acteoside revealed an increase in the level of tumor suppressor protein p53 as well as a decrease of kallikrein-related peptidase (KLK1, 2, 4, 9 and 10) gene level with no significant changes of the rest of KLK1–15 genes. Conclusions Acteoside exerts an antitumor effect possibly through its up-regulation of p53 levels as well as inhibition of KLK expression and angiogenesis. Acteoside could be useful as an adjunct in the treatment of advanced HCC in the clinic.

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Hepatocellular carcinoma: Mechanisms of progression and immunotherapy

Cited by 98 publications

References 166 publications

PRELP has prognostic value and regulates cell proliferation and migration in hepatocellular carcinoma

PRELP has prognostic value and regulates cell proliferation and migration in hepatocellular carcinoma

Current progress and prospect of immune checkpoint inhibitors in hepatocellular carcinoma (Review)

Acteoside as a potential therapeutic option for primary hepatocellular carcinoma: a preclinical study

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