Glypican 3 as a Serum Marker for Hepatoblastoma

Zhou, Shengmei; O’Gorman, Maurice R.G.; Yang, Fusheng; Andresen, Kevin; Wang, Larry

doi:10.1038/srep45932

Cited by 27 publications

(24 citation statements)

References 35 publications

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“…These expression profiles suggest that activation of hepatocyte proliferation and inhibition of differentiation are associated with HBL. Among the upregulated genes, DKK1 is an inhibitor of Wnt signaling, and GPC3 overexpression has been reported previously in HBL as well as nephroblastoma [19][20][21][22]. Therefore, these gene expression profiles seemed to be reliable, and the oncogenesis of HBL may depend on aberrant Wnt signaling and ontogenesis.…”

Section: Discussionmentioning

confidence: 91%

Gene expression profiling in hepatoblastoma cases of the Japanese Study Group for Pediatric Liver Tumors-2 (JPLT-2) trial

Kanawa¹,

Hiyama²,

Kawashima³

et al. 2019

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Background: Over the past two decades, significant improvements in the outcomes of children diagnosed with hepatoblastoma (HBL) have resulted from developments in diagnostic methods and treatments. However, the outcomes of some cases remain unfavorable, and others suffer from late complications caused by treatment. Procedure: We elucidated the genetic profile of HBLs to identify biological markers for diagnosis and to determine the grade of malignancy. RNA samples extracted from 53 specimens of fresh-frozen HBL and corresponding noncancerous liver tissues were used for gene expression profiling and pathway analysis. Results: In the comparison between HBL and noncancerous liver tissues, genes involved in several transcription pathways including glypican 3 and Wnt signaling pathway members were upregulated, whereas cytochrome p450 family genes were downregulated. The analyses of high-risk (metastatic) HBL and HBL progression or recurrence cases revealed upregulated expression of histone cluster genes and upregulation of RXR activators molecular signaling. Clustering analysis of the tumor samples revealed three distinct groups among the HBL cases. Conclusion: Aberrant expression of genes involved in tissue differentiation pathways may be related to the development of HBL, and such genes, including AFP, PGC, SPINK1, and NQO1, may be putative therapeutic targets for HBL progression

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Section: Discussionmentioning

confidence: 91%

Gene expression profiling in hepatoblastoma cases of the Japanese Study Group for Pediatric Liver Tumors-2 (JPLT-2) trial

Kanawa¹,

Hiyama²,

Kawashima³

et al. 2019

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“…Also, the expression level of GPC3 is correlated with prognosis [66][67][68][69]. In addition, GPC3 is also highly expressed in some other cancers such as hepatoblastoma [70], lung squamous cell carcinoma [71], ovarian yolk sac tumor [72], melanoma [73], and urothelial carcinoma [74]. Therefore, GPC3 is not only a specific biomarker and prognostic factor for HCC, but also a potential target for a variety of tumor treatments.…”

Section: Gpc3 As a Target For Clinical Diagnosis And Its Significancementioning

confidence: 99%

“…GPC3 is not only expressed on the surface of tumor cells, but also released into peripheral in soluble form (sGPC3). In combination with AFP, we can further improve the sensitivity in non-invasive diagnosis of liver tumors [5,33,70,75,76].…”

Section: Expression Of Gpc3 In Liver Cancer Tissuesmentioning

confidence: 99%

Glypican-3: A New Target for Diagnosis and Treatment of Hepatocellular Carcinoma

et al. 2020

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Liver cancer is the second leading cause of cancer-related deaths worldwide, and hepatocellular carcinoma is the most common type. The pathogenesis of hepatocellular carcinoma is concealed, its progress is rapid, its prognosis is poor, and the mortality rate is high. Therefore, novel molecular targets for hepatocellular carcinoma early diagnosis and development of targeted therapy are critically needed. Glypican-3, a cell-surface glycoproteins in which heparan sulfate glycosaminoglycan chains are covalently linked to a protein core, is overexpressed in HCC tissues but not in the healthy adult liver. Thus, Glypican-3 is becoming a promising candidate for liver cancer diagnosis and immunotherapy. Up to now, Glypican-3 has been a reliable immunohistochemical marker for hepatocellular carcinoma diagnosis, and soluble Glypican-3 in serum has becoming a promising marker for liquid biopsy. Moreover, various immunotherapies targeting Glypican-3 have been developed, including Glypican-3 vaccines, anti-Glypican-3 immunotoxin and chimeric-antigen-receptor modified cells. In this review, we summarize and analyze the structure and physicochemical properties of Glypican-3 molecules, then review their biological functions and applications in clinical diagnosis, and explore the diagnosis and treatment strategies based on Glypican-3.

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“…There has been an exploration of new targets in the management of hepatoblastoma including signal transducer and activator of transcription signaling 3 (STAT3) [71,72]; NOTCH receptors and their ligands [73]; PI3K/Akt, ERK and p38 signaling pathways [74]; GPC3 [75]; PIM Kinases [76]; ROCK1 [77]; mTOR and YAP [38]. Among these targets, Wnt/β-catenin has been more explored in different types of cancers including hepatoblastoma.…”

Section: Discussionmentioning

confidence: 99%

Wnt/β-catenin signaling as a useful therapeutic target in hepatoblastoma

et al. 2019

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Hepatoblastoma is a malignant tumor in the liver of children that generally occurs at the age of 2–3 years. There have been ample evidence from the preclinical as well as clinical studies suggesting the activation of Wnt/β-catenin signaling in hepatoblastoma, which is mainly attributed to the somatic mutations in the exon 3 of β-catenin gene. There is increased translocation of β-catenin protein from the cell surface to cytoplasm and nucleus and intracellular accumulation is directly linked to the severity of the cancer. Accordingly, the alterations in β-catenin and its target genes may be used as markers in the diagnosis and prognosis of pediatric live tumors. Furthermore, scientists have reported the therapeutic usefulness of inhibition of Wnt/β-catenin signaling in hepatoblastoma and this inhibition of signaling has been done using different methods including short interfering RNA (siRNA), miRNA and pharmacological agents. Wnt/β-catenin works in association with other signaling pathways to induce the development of hepatoblastoma including Yes-associated protein (YAP)1 (YAP-1), mammalian target of rapamycin (mTOR) 1 (mTOR-1), SLC38A1, glypican 3 (GPC3), nuclear factor κ-light-chain-enhancer of activated B cells (NF-kB), epidermal growth factor receptor, ERK1/2, tumor necrosis factor-α (TNF-α), regenerating islet-derived 1 and 3 α (REG1A and 3A), substance P (SP)/neurokinin-1 receptor and PARP-1. The present review describes the key role of Wnt/β-catenin signaling in the development of hepatoblastoma. Moreover, the role of other signaling pathways in hepatoblastoma in association with Wnt/β-catenin has also been described.

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Glypican 3 as a Serum Marker for Hepatoblastoma

Cited by 27 publications

References 35 publications

Gene expression profiling in hepatoblastoma cases of the Japanese Study Group for Pediatric Liver Tumors-2 (JPLT-2) trial

Gene expression profiling in hepatoblastoma cases of the Japanese Study Group for Pediatric Liver Tumors-2 (JPLT-2) trial

Glypican-3: A New Target for Diagnosis and Treatment of Hepatocellular Carcinoma

Wnt/β-catenin signaling as a useful therapeutic target in hepatoblastoma

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