Glypican-3 expression is correlated with poor prognosis in hepatocellular carcinoma (original) (raw)

Prognostic value and morphological findings of overexpression of glypican-3 in hepatocellular carcinoma

European Journal of Gastroenterology & Hepatology, 2022

Purpose: Hepatocellular carcinoma (HCC) is the seventh most common cancer all over the world and is second in cancer-related deaths.. In HCC, whose prognosis is still not good despite current treatments, there is a need for prognostic markers as well as early diagnosis. Glypican (GPC)-3 has been proposed as a potential serologic and histochemical marker speci c to HCC. The aim of this study was to determine the relationship between GPC3 overexpression and HCC prognosis and clinicomorphologic features. Patients and methods: In total 152 patients patients who were diagnosed as a result of hepatectomy, lobectomy, or liver transplantation were enrolled. The patients were divided into two groups as GPC3positive (>10%) and GPC3-negative (<10%). The demographic data of the patients ,tumor characteristics , survival times were recorded. Results: Survival was signi cantly lower in the GPC3+ group. In the multivariate analysis, hepatitis C, AFP, tumor number, tumor focality, portal vein tumor thrombosis, and GLP3 positivity were found to be independent risk factors on survival. Conclusion: Our study showing that GPC3 overexpression is a poor prognostic factor in HCC.GLP3 positivity were found to be independent risk factors on survival.

Biology and function of glypican-3 as a candidate for early cancerous transformation of hepatocytes in hepatocellular carcinoma

Oncology Reports, 2017

Glypican-3 (GPC-3), a transmembrane heparan sulfate proteoglycan (HSPG), has recently been investigated as a player in tissue-dependent cellular signaling, specifically as a regulator of growth. Noteworthy, the regulatory protein has been implicated in both stimulatory and inhibitory pathways involving cell growth. Initially, GPC-3 was thought to act as a cell cycle regulator, as a loss-of-function mutation in the gene caused a hyper-proliferative state known as Simpson-Golabi-Behmel (SGB) overgrowth syndrome. Additionally, certain cancer types have displayed a downregulation of GPC-3 expression. More recently, the protein has been evaluated as a useful marker for hepatocellular carcinoma (HCC) due to its increased expression in the liver during times of growth. In contrast, the GPC-3 marker is not detectable in normal adult liver. Immunotherapy that targets GPC-3 and its affiliated proteins is under investigation as these new biomarkers may hold potential for the detection and treatment of HCC and other diseases in which GPC-3 may be overexpressed. Studies have reported that an overexpression of GPC-3 in HCC predicts a poorer prognosis. This prognostic value further pushes the question regarding GPC-3's role in the regulation and progression of HCC. This review will summarize the current knowledge regarding the clinical aspects of GPC-3, while also synthesizing the current literature with the aim to better understand this molecule's biological interactions at a molecular level, not only in the liver, but in the rest of the body as well. Due to the existing gap in the literature surrounding GPC-3, we believe further investigation of function, structure and domains, cellular localization, and other subfields is warranted to evaluate the protein as a whole, as well as its part in the study of HCC. Contents 1. Introduction and structure of GPC-3 2. Expression pattern of GPC-3 in human and mouse 3. GPC-3 as a serum marker for early detection of HCC 4. GPC-3 in resection, regeneration and liver diseases 5. GPC-3 as a therapeutic target for HCC 6. GPC-3 and co-receptors 7. Conclusion

Prognostıc Value And Morphologıcal Fındıngs Of Overexpressıon Of Glypıcan-3 In Hepatocellular Carcınoma

Purpose: Hepatocellular carcinoma (HCC) is the seventh most common cancer all over the world and is second in cancer-related deaths. . In HCC, whose prognosis is still not good despite current treatments, there is a need for prognostic markers as well as early diagnosis. Glypican (GPC)-3 has been proposed as a potential serologic and histochemical marker specific to HCC. The aim of this study was to determine the relationship between GPC3 overexpression and HCC prognosis and clinicomorphologic features.Patients and methods: In total 152 patients patients who were diagnosed as a result of hepatectomy, lobectomy, or liver transplantation were enrolled. The patients were divided into two groups as GPC3-positive (>10%) and GPC3-negative (<10%). The demographic data of the patients ,tumor characteristics , survival times were recorded.Results: Survival was significantly lower in the GPC3+ group. In the multivariate analysis, hepatitis C, AFP, tumor number, tumor focality, portal ve...

Upregulation of Glypican-3 expression in hepatocellular carcinoma but downregulation in cholangiocarcinoma indicates its differential diagnosis value in primary liver cancers

Liver International, 2005

Background/Aim: Expression alteration of Glypican-3 (GPC3) is associated with several malignancies and has been identified as an overexpressed gene in hepatocellular carcinoma (HCC). In this study GPC3 expression in intrahepatic chanlangiocarcinoma (ICC), gallbladder cancer and HCC was quantitatively detected. Methods: Real-time quantitative reverse transcription polymerase chain reaction was used to detect the expression level of GPC3. Results: GPC3 expression was elevated more than two-fold in HCC compared with adjacent tissue in 90 of 100 HCC cases. The average expression level of GPC3 was significantly higher in HCC than that in adjacent liver tissues (Po0.0001). Only in four of 21 ICC cases GPC3 expression was upregulated more than two-fold in tumor tissues. GPC3 expression was downregulated in gallbladder cancer in 12 of 13 cases and the average expression level was significantly lower than that in normal gallbladder tissues (Po0.05). Conclusion: The different expression patterns of GPC3 in HCC and ICC suggested that it might play a different role in theses tumors and could serve as a biomarker for differential diagnosis of HCC and ICC.

GPC3 reduces cell proliferation in renal carcinoma cell lines

BMC Cancer, 2014

Background: Glypican 3 (GPC3) is a member of the family of glypican heparan sulfate proteoglycans (HSPGs). The GPC3 gene may play a role in controlling cell migration, negatively regulating cell growth and inducing apoptosis. GPC3 is downregulated in several cancers, which can result in uncontrolled cell growth and can also contribute to the malignant phenotype of some tumors. The purpose of this study was to analyze the mechanism of action of the GPC3 gene in clear cell renal cell carcinoma.

Glypican-3, overexpressed specifically in human hepatocellular carcinoma, is a novel tumor marker

Biochemical and Biophysical Research Communications, 2003

With the global pandemic of hepatitis B and C infections, the incidence of Hepatocellular carcinoma (HCC) is rapidly increasing world wide. We identified glypican-3 (GPC3), a novel oncofetal gene over-expressed specifically in human HCC, as based on data of cDNA microarrays. As GPC3 is a GPI-anchored membrane protein and could be secreted, we attempted to detect secreted GPC3 protein in sera from HCC patients using Western blotting and ELISA. GPC3 protein was positive in sera of 40.0% (16/40) of HCC patients, and negative in sera from subjects with liver cirrhosis (LC) (0/13), chronic hepatitis (CH) (0/34), and healthy donors (0/60). All subjects were Japanese. Although 12 of 40 HCC patients were negative for both alpha-fetoprotein (AFP) and PIVKA-II well known tumor markers of HCC, four of these were GPC3-positive in the sera. We also observed vanishing GPC3 protein in the sera of three patients after the surgical treatment for HCC. On the other hand, immunohistochemical analysis revealed that HCC expressed GPC3 protein in all 14 HCC patients tested. In conclusion, GPC3, as defined in this study was shown to be a useful tumor marker for cancer-diagnosis for large numbers of patients with HCC.

Expression of glypican 3 in hepatoblastoma: an immunohistochemical study of 65 cases

Human Pathology, 2008

Glypican 3 is a heparin sulfate proteoglycan bound to the cell surface that is theorized to participate in cell signaling, resulting in embryonic cell growth and differentiation. The GPC3 gene is mutated in Simpson-Golabi-Behmel syndrome, whose features include numerous developmental abnormalities, tissue overgrowth, and an increased risk for embryonal malignancies, including hepatoblastoma. GPC3 has been detected in hepatic stem cells and was recently identified as one of the most overexpressed genes in hepatoblastoma by microarray analysis. The purpose of this study was to analyze the expression of GPC3 in a large series of hepatoblastoma using immunohistochemistry to assess its use as a diagnostic marker. The GPC3 immunoreactivity was semiquantitatively evaluated in 65 cases of hepatoblastoma. In addition, histologic patterns in each tumor were individually assessed for immunoreactivity. All 65 hepatoblastomas had cytoplasmic immunoreactivity for GPC3 with greater than 90% of cases showing strong, diffuse positivity. There was no reactivity in benign liver tissue. Fetal, embryonal, and small cell undifferentiated patterns were diffusely positive in almost all cases, whereas mesenchymal and teratoid patterns were nearly all negative. The high GPC3 expression consistently demonstrated in this study suggests that GPC3 may play a role in the tumorigenesis of hepatoblastoma.

Expression of Glypican-3 (GPC3) in Malignant and Non-malignant Human Breast Tissues

The Open Cancer Journal, 2015

Specific reports have linked GPC3 with cancer. Its usefulness as a marker has been proved for hepatocarcinoma, melanoma and ovary carcinoma. However, there are no studies analyzing GPC3 usefulness as a biomarker in mammary tumors. The aim of this work was to analyze GPC3 expression in breast tissues and to determine whether it might be useful as a biomarker in breast cancer patients. Expression level of GPC3 mRNA in Brazilian and Argentine human breast tumor (n=121) and peritumoral "normal" tissue (n=77) samples was analyzed using qRT-PCR. GPC3 protein expression was analyzed from 69 breast cancer and 10 peritumoral samples using IHC. Statistical analyses were done to evaluate the clinical-pathological significance of GPC3 expression. We found that Brazilian and Argentine populations are statistically different regarding GPC3 mRNA expression. In Argentine patients a lower GPC3 mRNA expression was found in tumors as compared to peritumoral tissues. No association was found between GPC3 mRNA and protein expression and the clinical-pathological parameters. The Kaplan-Meier curves suggested that elevated levels of GPC3 mRNA are associated with relapse. Our results indicate differential expression of GPC3 in mammary tumors in comparasion to normal breast tissues. They also suggest the potential role of GPC3 as a biomarker and the importance of deepening the study.

Glypican 3-expressing gastric carcinoma: Distinct subgroup unifying hepatoid, clear-cell, and α-fetoprotein-producing gastric carcinomas

Cancer Science, 2009

Gypican-3 (GPC3) has been recognized as an oncofetal protein in hepatic neoplasms and yolk sac tumors. To characterize a distinct subgroup of gastric carcinoma (GC) expressing GPC3 (GPC3-GC), primary and metastatic GC tissues were evaluated by immunohistochemistry with special focus on their related entities: hepatoid, clear-cell, and afetoprotein-producing GC. GPC3-GC was defined as focal GPC3-GC when 10-49% of neoplastic cells were positive, and as diffuse GPC3-GC when more than 50% of cells were positive. Among 926 GC cases, 101 (11%) were GPC3-GC, of which 45 were diffuse and 56 were focal GPC3-GC. Specific histological patterns, such as the hepatoid and clearcell patterns, were frequently observed in diffuse GPC3-GC (38 and 49%, respectively) and in focal GPC3-GC (4 and 25%, respectively), whereas these patterns were extremely rare in GPC3-negative GC. Immunoreactive a-fetoprotein was only identified in GPC3-GC (38% of diffuse and 14% of focal GPC3-GC). Both diffuse and focal GPC3-GC showed nodal metastasis more frequently (67 and 55%, respectively) than GPC3-negative GC (34%), and the diffuse GPC3-GC had significantly more T2-4 and M1 stage cases. GPC3 immunostaining was present in 57 out of 61 nodal metastases (93%) and in all four liver metastases examined. Importantly, diffuse GPC3 expression was observed in the liver metastasis, even if the primary tumor was focal GPC3-GC. GPC3-GC is a distinctive group of GC, which unifies hepatoid, clear-cell, and a-fetoprotein-producing GC. GPC3 is expected to be a target of forthcoming immunotherapy for a patient bearing this specific type

Glypican-3 in hepatocellular carcinoma

HCV infection patients without any complications, group III: 100 HCV infected patients complicated with cirrhosis and group IV: 150 HCV infected patients complicated with (90 localized and 60 metastatic) HCC. Detection of serum GPC3 and alpha-fetoprotein using an enzyme-linked immunosorbent assay (ELISA) were done to all subjects. Results: When analysis of variance was done between the four groups, a highly statistical significant difference was found between these groups regarding the mean serum levels of AFP and GPC-3 where the highest increase of three markers were found in the HCC group. The combined AFP and Glypican-3 improve the sensitivity and specificity of AFP alone. Conclusions: GPC-3 could be a sensitive, specific and accurate marker for early detection of HCC diagnosis. 