Dataset Information

Molecular Targets, Pathways, and Therapeutic Implications for Hepatocellular Carcinoma.

ABSTRACT: Hepatocellular carcinoma (HCC) represents one of the leading causes of cancer mortality worldwide. While significant advances have been made for the treatment of advanced hepatocellular carcinoma in the past few years, the prognosis remains poor and effective biomarkers to guide selection of therapies remain noticeably absent. However, several targeted therapies have been approved in the past few years that have improved the outlook for this disease. In this review, we will highlight the recent therapies approved for the treatment of advanced HCC and discuss promising therapeutic options, targets, and pathways for drug development and consideration for future clinical trials.

SUBMITTER: Gong J

PROVIDER: S-EPMC7432744 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Publications

Molecular Targets, Pathways, and Therapeutic Implications for Hepatocellular Carcinoma.

Gong Jun J Chuang Jeremy J Cho May M Toomey Kyra K Hendifar Andrew A Li Daneng D

International journal of molecular sciences 20200723 15

Hepatocellular carcinoma (HCC) represents one of the leading causes of cancer mortality worldwide. While significant advances have been made for the treatment of advanced hepatocellular carcinoma in the past few years, the prognosis remains poor and effective biomarkers to guide selection of therapies remain noticeably absent. However, several targeted therapies have been approved in the past few years that have improved the outlook for this disease. In this review, we will highlight the recent ...[more]

PMID: 32718047

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Project description:Immunosuppressive tumor microenvironment in hepatocellular carcinoma (HCC) is critical in tumor development. C-type (Ca2+ -dependent) lectin (CLEC) receptors, essential in innate pattern recognition, have potential regulatory effects on immune cell trafficking and modulatory effects on cancer cell activity. However, information on the expression and prognostic value of CLECs in HCC is scanty. Herein, we explored the potential role of CLECs in HCC based on TCGA, ONCOMINE, GEPIA, UALCAN, cBioPortal, Metascape, TRRUST, and TIMER databases. Results demonstrated a significantly higher mRNA level of CLEC4A and CLEC4L in HCC tissues than normal liver tissues. Contrarily, we found significantly low CLEC4G/H1/H2/M expression in HCC tissues. The IHC analysis revealed the following: Absence of CLEC4A/J/K/M in normal and liver cancer tissues; high CLEC4C expression in HCC tissues; low expression and zero detection of CLEC4D/E/H1/H2/L in HCC tissues and normal tissues, respectively. And the HepG2 and LX-2 were used to verify the expression level of CLEC4s via qRT-PCR in vitro. Furthermore, the expression of CLEC4H1 (ASGR1) and CLEC4H2 (ASGR2) exhibited a significant relation to clinical stages. However, the expression of CLEC4A, CLEC4D, CLEC4E, CLEC4J (FCER2), CLEC4K (CD207), CLEC4G, CLEC4H1, CLEC4M, and CLEC4H2 decreased with tumor progression. Patients expressing higher CLEC4H1/H2 levels had longer overall survival than patients exhibiting lower expression. Moreover, CLEC4A/D/E/J/K/G/H1/M/H2 had significant down-regulated levels of promoter methylation. The expression level of CLEC4s was correlated with the infiltration of B cells, CD8 + T cells, CD4 + T cells, macrophage cells, neutrophil cells, and dendritic cells. Functional analysis revealed the potential role of CLECL4s in virus infection, including COVID-19. Also, hsa-miR-4278 and hsa-miR-324-5p, two potential miRNA targets of CLEC4s, were uncovered. This article demonstrates that CLEC4 is crucial for the development of HCC and is associated with infiltration of various immune cells, providing evidence for new immunotherapy targets in HCC.

Dataset Information

Molecular Targets, Pathways, and Therapeutic Implications for Hepatocellular Carcinoma.

Publications

Molecular Targets, Pathways, and Therapeutic Implications for Hepatocellular Carcinoma.

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