Glypican-3: From the mutations of Simpson–Golabi–Behmel genetic syndrome to a tumor marker for hepatocellular carcinoma

Jakubovic, Baruch D.; Jothy, Serge

doi:10.1016/j.yexmp.2006.10.010

Cited by 38 publications

(43 citation statements)

References 54 publications

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“…Our results are in agreement with many other researchers (Nakatsura et al, 2003;Hippo et al, 2004;Nakatsura et al, 2005;Jackbovic et al, 2007). Thus, the simultaneous use of both markers significantly increases the sensitivity without compromising the specificity of any.…”

Section: Discussionsupporting

confidence: 93%

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Can Glypican3 be Diagnostic for Early Hepatocellular Carcinoma among Egyptian Patients?

Abdelgawad

Mossallam²,

Radwan³

et al. 2013

Asian Pacific Journal of Cancer Prevention

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Background: Because of the high prevalence of hepatocellular carcinoma (HCC) in Egypt, new markers with better diagnostic performance than alpha-feto protein (AFP) are needed to help in early diagnosis. The aim of this work was to compare the clinical utility of both serum and mRNA glypican3 (GPC3) as probable diagnostic markers for HCC among Egyptian patients. Materials and Methods: A total of 60 subjects, including 40 with HCC, 10 with cirrhosis and 10 normal controls were analyzed for serum GPC3 (sGPC3) by ELISA. GPC-3 mRNA from circulating peripheral blood mononuclear cells was amplified by RT-PCR. Both markers were compared to some prognostic factors of HCC, and sensitivity of both techniques was compared. Results: Serum glypican-3 and AFP were significantly higher in the HCC group compared to cirrhotic and normal controls (p<0.001). Sensitivity and specificity were (95% each) for sGlypican-3, (82.5% and 85%) for AFP, and (100% and 90%) for Glypican3 mRNA , and (80% and 95%) for double combination between sGPC3 and AFP respectively. Conclusion: Both serum GPC-3 and GPC-3mRNA are promising diagnostic markers for early detection of HCC in Egyptian patients. RT-PCR proved to be more sensitive (100%) than ELISA (95%) in detecting glypican3.

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Section: Discussionsupporting

confidence: 93%

“…It is the 2 nd most common cancer site among males and 7 th among females (NCI Cancer Registry, 2002-2007). The rising rates of HCC in Egypt are due to the high prevalence of hepatitis B virus (HBV) and hepatitis C virus infection (HCV) (25.9% and 78.5%) among Egyptian population.…”

Section: Introductionmentioning

confidence: 99%

Can Glypican3 be Diagnostic for Early Hepatocellular Carcinoma among Egyptian Patients?

Abdelgawad

Mossallam²,

Radwan³

et al. 2013

Asian Pacific Journal of Cancer Prevention

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“…GPC3 is a gene involved in various human diseases including type 1 Simpson-Golabi-Behmel syndrome and Wilms tumors. Moreover, GPC3 is overexpressed in hepatocellular carcinoma (HCC) and hepatoblastoma (Jakubovic and Jothy 2007), in which its expression correlates with tumor aggressiveness and poor prognosis (Shirakawa et al 2009). To characterize the miRNAs regulating GPC3 expression in HCC-derived cells, we screened a library of 876 human mature miRNA mimics using the GPC3 3 ′ UTR as a bait (Maurel et al 2013).…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-1291-mediated silencing of IRE1α enhances Glypican-3 expression

Maurel

Dejeans

Taouji

et al. 2013

RNA

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MicroRNAs (miRNA) are generally described as negative regulators of gene expression. However, some evidence suggests that they may also play positive roles. As such, we reported that miR-1291 leads to a GPC3 mRNA expression increase in hepatoma cells through a 3 ′ untranslated region (UTR)-dependent mechanism. In the absence of any direct interaction between miR-1291 and GPC3 mRNA, we hypothesized that miR-1291 could act by silencing a negative regulator of GPC3 mRNA expression. Based on in silico predictions and experimental validation, we demonstrate herein that miR-1291 represses the expression of the mRNA encoding the endoplasmic reticulum (ER)-resident stress sensor IRE1α by interacting with a specific site located in the 5 ′ UTR. Moreover, we show, in vitro and in cultured cells, that IRE1α cleaves GPC3 mRNA at a 3 ′ UTR consensus site independently of ER stress, thereby prompting GPC3 mRNA degradation. Finally, we show that the expression of a miR-1291-resistant form of IRE1α abrogates the positive effects of miR-1291 on GPC3 mRNA expression. Collectively, our data demonstrate that miR-1291 is a biologically relevant regulator of GPC3 expression in hepatoma cells and acts through silencing of the ER stress sensor IRE1α.

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“…8 In this preand postnatal overgrowth syndrome, the glypican-3 gene is functionally inactivated by either point mutations or micro-deletions. 9 In addition to visceral and skeletal abnormalities, SimpsonGolabi-Behmel patients have increased incidence of embryonal tumors (Wilms' tumor, neuroblastoma and hepatoblastoma). 8,10 This combination of findings suggested that glypican-3 has an inhibitory effect on cell proliferation and could function as a tumor-suppressor gene.…”

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confidence: 99%

Glypican-3 is overexpressed in lung squamous cell carcinoma, but not in adenocarcinoma

et al. 2008

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Glypican-3 is a membrane-bound proteoglycan whose expression has been linked to malignancies through the existence of both mutations and aberrant protein expression. Reports on glypican-3 expression in lung cancer were limited, with some evidence for loss of expression, which suggested a tumor-suppressor role. We sought to evaluate glypican-3 expression in lung cancer at the protein and mRNA levels and correlate it with clinical, histological and genomic characteristics such as RAS mutation status. We used immunohistochemistry on tissue microarray to study glypican-3 expression in 97 patients, evaluated glypican-3 mRNA levels by quantitative polymerase chain reaction in 143 patients and identified RAS mutations by allele-specific oligonucleotide hybridization. We correlated the results with clinical and histological data. Glypican-3 immunostaining was negative in all normal lung tissues, but positive in 23% of lung carcinoma samples. High protein and mRNA expression was associated with squamous histology (positive stain in 55% of squamous cell carcinoma vs 8% of adenocarcinoma, Po0.0001 for both immunostaining and mRNA). RAS mutations were highly associated with adenocarcinoma and low glypican-3 mRNA expression (Po0.0001 for both). Among smokers, glypican-3 mRNA expression was reduced in adenocarcinoma patients (P ¼ 0.013), and was elevated in those with squamous cell carcinoma (P ¼ 0.03, interaction P ¼ 0.0009). These opposing associations also correlated with the smoking burden. Patients with tumors staining positively for glypican-3 smoked significantly more than patients with tumors staining negatively (P ¼ 0.013). No association was found between glypican-3 expression and patient outcome. In conclusion, glypican-3 was overexpressed in cancerous compared with normal lung tissue. Adenocarcinoma and squamous cell carcinoma had differential expression of glypican-3, with predilection to squamous cell carcinoma patients who smoked. Glypican-3 expression in squamous cell carcinoma as an oncofetal protein renders it a potential candidate marker for early detection of lung squamous cell carcinoma.

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Glypican-3: From the mutations of Simpson–Golabi–Behmel genetic syndrome to a tumor marker for hepatocellular carcinoma

Cited by 38 publications

References 54 publications

Can Glypican3 be Diagnostic for Early Hepatocellular Carcinoma among Egyptian Patients?

Can Glypican3 be Diagnostic for Early Hepatocellular Carcinoma among Egyptian Patients?

MicroRNA-1291-mediated silencing of IRE1α enhances Glypican-3 expression

Glypican-3 is overexpressed in lung squamous cell carcinoma, but not in adenocarcinoma

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