AIM:To evaluate the diagnostic value of glypican-3(GPC3) in serum and liver for primary hepatocellular carcinoma(HCC).METHODS:Serum levels of GPC3 and α-fetoprotein(AFP) were measured in 75 patients with primary HCC ...AIM:To evaluate the diagnostic value of glypican-3(GPC3) in serum and liver for primary hepatocellular carcinoma(HCC).METHODS:Serum levels of GPC3 and α-fetoprotein(AFP) were measured in 75 patients with primary HCC and 32 patients with liver cirrhosis.Expression of GPC3 and AFP in 58 HCC and 12 cirrhotic specimens was detected with immunohistochemical staining.RESULTS:When the cut-off value of serum GPC3 was set at 300 ng/L,its sensitivity and specificity for HCC were 47.0% and 93.5%,respectively.Among the 14 patients with HCC at stage according to the Barcelona Clinic Liver Cancer staging system,the serum GPC3 level was higher than 300 ng/L in 50%(7/14) patients,the serum AFP level was not ≥ 400 μg/L in any patient.Combined serum AFP and GPC3 significantly increased the sensitivity to the diagnosis of HCC.The GPC3 expression was detected in cytoplasm of HCC cells but not in hepatocytes and bile ducts of benign tumors.Among the 58 HCC patients,the GPC3 was expressed in 100%(28/28) patients with their serum AFP level ≥ 400 μg/L,and in 90%(27/30) patients with their AFP level < 400 μg/L,respectively.The GPC3 was weakly or negatively expressed in all paracarcinomatous and cirrhotic tissue samples.AFP positive HCC cells were only found in 1 out of the 58 HCC patients.CONCLUSION:GPC3 protein is a sensitive and specific serum marker for diagnosis of early HCC.Its expression in liver tissues can be used to discriminate tumor cells from benign hepatic cells.展开更多
BACKGROUND:Hepatocellular carcinoma (HCC) is characterized by a multi-cause,multi-stage and multi-focus process of tumor progression.Its prognosis is poor and early diagnosis is of utmost importance.This study was und...BACKGROUND:Hepatocellular carcinoma (HCC) is characterized by a multi-cause,multi-stage and multi-focus process of tumor progression.Its prognosis is poor and early diagnosis is of utmost importance.This study was undertaken to investigate the dynamic expression of oncofetal antigen glypican-3 (GPC-3) and GPC-3 mRNA in hepatocarcinogenesis and to explore their early diagnostic value for HCC.METHODS:A hepatoma model was induced in male Sprague-Dawley rats with 0.05% 2-fluorenylacetamide and confirmed by hematoxylin and eosin staining and gamma-glutamyltransferase (GGT) expression.Total RNA was purified and transcribed into cDNA by reverse transcription.Fragments of the GPC-3 gene were amplified by nested RT-PCR,and confirmed by sequencing.GPC-3 was analyzed by immunohistochemistry,Western blotting or ELISA.RESULTS:Positive GPC-3 expression showed as brown granule-like staining localized in the cytoplasm.Histological examination of hepatocytes revealed three morphological stages of granule-like degeneration,atypical hyperplasia (precancerous),and cancer formation,with a progressive increase of liver total RNA and GGT expression.The incidence of liver GPC-3 mRNA and GPC-3,and serum GPC-3 was 100%,100% and 77.8% in the HCC group,100%,100%,and 66.7% in the precancerous group,83.3%,83.3%,and 38.9% in the degeneration group,and no expression in the liver or blood of the control group,respectively.There was a positive correlation between liver GPC-3 mRNA and total RNA level (r=0.475,P<0.05) or liver GPC-3 (r=1.0,P<0.001) or serum GPC-3 (r= 0.994,P<0.001).CONCLUSION:Abnormal oncofetal antigen GPC-3 and GPC-3 mRNA expression in hepatocarcinogenesis may be promising molecular markers for early diagnosis of HCC.展开更多
Glypican-3(GPC3)is a cell surface oncofetal proteoglycan that is anchored by glycosylphosphatidylinositol.Whereas GPC3 is abundant in fetal liver,its expression is hardly detectable in adult liver.Importantly,GPC3is o...Glypican-3(GPC3)is a cell surface oncofetal proteoglycan that is anchored by glycosylphosphatidylinositol.Whereas GPC3 is abundant in fetal liver,its expression is hardly detectable in adult liver.Importantly,GPC3is overexpressed in hepatocellular carcinoma(HCC),and several immunohistochemical studies reported that overexpression predicts a poorer prognosis for HCC patients.Therefore,GPC3 would serve as a useful molecular marker for HCC diagnosis and also as a target for therapeutic intervention in HCC.Indeed,some immunotherapy protocols targeting GPC3 are under investigations;those include humanized anti-GPC3cytotoxic antibody,peptide vaccine and immunotoxin therapies.When considering the clinical requirements for GPC3-targeting therapy,companion diagnostics to select the appropriate HCC patients are critical,and both immunohistochemical analysis of tissue sections and measurement of serum GPC3 level have been suggested for this purpose.This review summarizes current knowledge regarding the clinical implication of GPC3detection and targeting in the management of patients with HCC.展开更多
AIM:To clarify the association of glypican-3(GPC3)expression with Wnt and other growth signaling molecules in hepatocellular carcinoma(HCC). METHODS:Expression of GPC3,Wnt,matrix metalloproteinases(MMPs),sulfatase(SUL...AIM:To clarify the association of glypican-3(GPC3)expression with Wnt and other growth signaling molecules in hepatocellular carcinoma(HCC). METHODS:Expression of GPC3,Wnt,matrix metalloproteinases(MMPs),sulfatase(SULF)1,SULF2,and other growth signaling molecules was analyzed in HCC cell lines and tissue samples by real-time reverse transcriptionpolymerase chain reaction,immunoblotting,and/or immunostaining.Expression of various genes in GPC3 siRNA-transfected HCC cells was analyzed. RESULTS:GPC3 was overexpressed in most HCCs at mRNA and protein levels and its serum levels weresignificantly higher in patients with HCC than in non- HCC subjects(P<0.05).Altered expressions of various MMPs and growth signaling molecules,some of which were correlated with GPC3 expression,were observed in HCCs.Down-regulation of GPC3 expression by siRNA in GPC3-overexpressing HCC cell lines resulted in a significant decrease in expressions of MMP2,MMP14,fibroblast growth factor receptor 1,insulin-like growth factor 1 receptor.GPC3 expression was significantly correlated with nuclear/cytoplasmic localization ofβ-catenin. CONCLUSION:These results suggest that GPC3,in conjunction with MMPs and growth signaling molecules, might play an important role in the progression of HCC.展开更多
BACKGROUND: The prognosis of hepatocellular carcinoma (HCC) is poor and its early diagnosis is of the utmost importance. This study aimed to investigate the values of glypican-3 (GPC-3) expression in the liver and ser...BACKGROUND: The prognosis of hepatocellular carcinoma (HCC) is poor and its early diagnosis is of the utmost importance. This study aimed to investigate the values of glypican-3 (GPC-3) expression in the liver and sera and its gene transcription for diagnosis and monitoring of metastasis of HCC. METHODS: Liver GPC-3 was analyzed in HCC tissues from 36 patients by immunohistochemistry and Western blotting. GPC-3 mRNA from circulating peripheral blood mononuclear cells from 123 HCC patients or 246 patients with other diseases or 36 HCC tissues was amplified by RT-PCR, quantitative realtime PCR, and confirmed by DNA sequencing. Circulating GPC-3 level was detected by ELISA. RESULTS: The increasing expression of GPC-3 was observed from non-cancerous to cancerous tissues, with brown granule-like staining localized in tumor parts of atypical hyperplasia and HCC formation. The positive rate of GPC-3 was 80.6% in HCC, 41.7% in their paracancerous tissues, and none in distal cancerous tissues (P【0.001), with no significant difference in differentiation grade and tumor number except for size (Z=2.941, P=0.003). Serum GPC-3 was detected only in HCC (52.8%) and significant difference was found between GPC-3 and tumor size (χ2 =6.318, P=0.012) or HBV infection (χ2 =23.362, P【0.001). Circulating GPC-3 mRNA was detected in 70.7% of HCC tissues, with relation to TNM stage, periportal cancerous embolus, and extra-hepatic metastasis (P【0.001). The combination ofcirculating GPC-3, GPC-3 mRNA and alpha-fetoprotein is of complementary value for HCC diagnosis (94.3%). CONCLUSION: Both GPC-3 overexpression and GPC-3 mRNA abnormality could be used as markers for the diagnosis of HCC and monitoring its metastasis.展开更多
Glypican-3(GPC3) is a promising tumor marker for hepatocellular carcinoma(HCC) diagnosis with high sensitivity and specificity.The aim of this study was to establish an immunohistochemical detection method for GPC3 us...Glypican-3(GPC3) is a promising tumor marker for hepatocellular carcinoma(HCC) diagnosis with high sensitivity and specificity.The aim of this study was to establish an immunohistochemical detection method for GPC3 using the 7D11 monoclonal antibody(7D11 mAb) and evaluate its application for HCC diagnosis.The feasibility of the 7D11 mAb was evaluated by immunohistochemistry performed on adjacent normal liver and intrahepatic cholangiocarcinoma(ICC) samples,Furthermore,the serum GPC3 levels were evaluated in 40 HCC patients,7 ICC patients and 50 healthy donors.The results showed that GPC3 was expressed in 85% of HCC tissues(34/40),but was undetectable in ICC tissues and adjacent normal tissues.GPC3 was significantly increased in the serum of HCC patients(17/40,42.5%) but was undetectable in the serum of ICC patients(0/7,0%) and healthy donors(0/50,0%).This prospective study evaluated the clinical usefulness of 7D11 mAb for GPC3 detection in HCC patients.In conclusion,the use of 7D11 mAb might be good for GPC3 large-scale applications for clinical diagnosis of HCC.展开更多
AIM:To investigate the diagnostic value of glypican-3(GPC3) and its relationship with hepatocellular carcinoma(HCC) recurrence after liver transplantation.METHODS:HCC tissue samples(n = 31) obtained from patients who ...AIM:To investigate the diagnostic value of glypican-3(GPC3) and its relationship with hepatocellular carcinoma(HCC) recurrence after liver transplantation.METHODS:HCC tissue samples(n = 31) obtained from patients who had undergone liver transplantation were analyzed.GPC3 mRNA and protein expression were analyzed by TaqMan real-time reverse transcription-polymerase chain reaction and immunohistochemistry.Correlation between the GPC3 expression and clinicopathological features was analyzed.The potential prognostic value of GPC3 was investigated by comparing recurrence-free survival between HCC patients with and without GPC3 expression.RESULTS:Using a cutoff value of 3.5 × 10-2,20 of 31 cancerous tissues had expression values of > 3.5 × 10-2,whereas 3 of 31 adjacent non-neoplastic parenchyma and 0 of 20 control liver tissues had expression values of > 3.5 × 10-2(P < 0.001).GPC3 protein was immunoexpressed in 68% of cancerous tissues,but not in adjacent non-neoplastic parenchyma and control liver tissues.Vascular invasion was significantly related to GPC3 expression(P < 0.05).Recurrence-free survival was significantly longer for patients without GPC3 mRNA overexpression(> 3.5 × 10-2) and those without vascular invasion(P < 0.05 for both).CONCLUSION:GPC3 expression may serve as a valuable diagnostic marker for HCC.GPC3 mRNA overexpression may be an adverse indicator for HCC patients after liver transplantation.展开更多
AIM: To investigate the prognostic and clinicopathological significance of glypican-3 (GPC3) overexpression in hepatocellular carcinoma (HCC). METHODS: Publications were searched using PubMed, EMBASE, the Cochrane Lib...AIM: To investigate the prognostic and clinicopathological significance of glypican-3 (GPC3) overexpression in hepatocellular carcinoma (HCC). METHODS: Publications were searched using PubMed, EMBASE, the Cochrane Library and the Chinese Biomedical Literature Database up to March 2013. Inclusion and exclusion criteria were established to screen eligible studies for meta-analysis. The hazard ratios (HRs) of the eligible studies were pooled using RevMan 5.2 software to evaluate the impact of GPC3 overexpression on overall survival (OS) and disease-free survival (DFS) in HCC patients. The correlation between GPC3 expression and clinicopathological parameters of HCC was also analyzed. RESULTS: A total of five studies with 493 patients were included in the meta-analysis. The combined HRs indicated that GPC3 overexpression can predict poor OS (n = 362 in 3 studies, HR = 2.18, 95%CI: 1.47-3.24, Z = 3.86, P = 0.0001) and DFS (n = 325 in 3 studies, HR = 2.05, 95%CI: 1.43-2.93, Z = 3.94, P < 0.0001) in HCC patients without heterogeneity. Egger's and Begg's tests were applied to detect publication bias, and the results showed that there was no evidence of publication bias detected in the OS studies (the P value for Egger's test was 0.216) or DFS studies (the P value for Egger's test was 0.488). The combined odds ratios (ORs) suggested that GPC3 expression tends to be associated with tumor vascular invasion (OR = 2.74, 95%CI: 1.15-6.52, P = 0.02), hepatic cirrhosis (OR = 2.10, 95%CI: 1.31-3.36, P = 0.002), poor tumor differentiation (OR = 0.22, 95%CI: 0.13-0.40, P < 0.00001) and advanced TNM stage (OR = 0.31, 95%CI: 0.18-0.51, P < 0.00001). CONCLUSION: From this study, we conclude that GPC3 overexpression tends to be associated with a poor prognosis (poor OS or DFS) in HCC. (C) 2014 Baishideng Publishing Group Inc. All rights reserved.展开更多
BACKGROUND： The carcinogenesis of hepatocellular car- cinoma （HCC） is a multi-factorial, multi-step and complex process. Early diagnosis and effective treatments are of utmost importance. This review summarized the...BACKGROUND： The carcinogenesis of hepatocellular car- cinoma （HCC） is a multi-factorial, multi-step and complex process. Early diagnosis and effective treatments are of utmost importance. This review summarized the recent studies of on- cofetal glypican-3 （GPC-3）, a membrane-associated heparan sulfate proteoglycan, in the diagnosis and treatment of HCC. DATA SOURCES： English-language reports published from Iune 2001 to September 2014 were searched from MEDLINE. The key words searched included： GPC-3, biomarker, target and HCC. The sensitivity, specificity, positive and negative predictive values were extracted, and the effect of GPC-3 tar- geted therapy on HCC was also evaluated. RESULTS： GPC-3 plays a crucial role in HCC cell prolifera- tion and metastasis. It mediates oncogenesis involving signal- ing pathways during hepatocyte malignant transformation. GPC-3 expression is increased in atypical hyperplasia and cancerous tissues. GPC-3 levels in HCC patients are related to HBV infection, TNM stage, periportal cancerous embolus, and extrahepatic metastasis. The diagnostic accuracy of the combination of serum GPC-3 and alpha-fetoprotein in HCC is up to 94.3%. Down-regulation of GPC-3 with specific siRNA or anti-GPC-3 antibody alters cell migration, metastasis and invasion behaviors. The nude mice xenograft tumor growth is inhibited by silencing GPC-3 gene transcription.CONCLUSION： Oncofetal GPC-3 is a highly specific biomark- er for the diagnosis of HCC and a promising target molecule for HCC gene therapy.展开更多
BACKGROUND：Glypican-3（GPC-3）is frequently overexpressed in hepatocellular carcinoma（HCC）.Recent studies have shown that GPC-3 is a highly efficient diagnostic biomarker of HCC and an indicator of poor prognosis i...BACKGROUND：Glypican-3（GPC-3）is frequently overexpressed in hepatocellular carcinoma（HCC）.Recent studies have shown that GPC-3 is a highly efficient diagnostic biomarker of HCC and an indicator of poor prognosis in HCC patients who have undergone hepatectomy.However,its prognostic value in patients with HBV-associated HCC after liver transplantation（LT）is not clear.The present study is to evaluate the prognostic value of GPC-3 in patients with HBV-associated HCC after LT.METHODS： A cohort of 104 HCC patients with HBV-associ- ated cirrhosis who had undergone LT at our hospital between 2002 and 2011 were enrolled in this study. Samples of HCC were taken from these patients. GPC-3 protein expression was detected in paraffin-embedded specimens using immunohis- tochemistry. All related clinical data were obtained from the China Liver Transplant Registry. The relationship between GPC-3 expression and clinicopathological parameters was analyzed. Univariate and multivariate Cox-regression analyses were used to identify risk factors for poor prognosis. RESULTS： GPC-3 was expressed in samples from 74 （71.2%） of the 104 patients. GPC-3 was expressed only in HCC cells. Positive staining was correlated with tumor size （P=0.004）, encapsulation （P=0.018）, pathological stage （P--0.027）, portal vein invasion （P=0.043）, tumor differentiation （P=0.002） and the Milan criteria （P=0.016）. The 5-year survival rate and dis- ease-free survival rate of patients with GPC-3-positive were lower than those （38.2% vs 75.4%, P〈0.001; 30.8% vs 69.7%, P=0.001） of patients with GPC-3-negative. Multivariate Coxregression analysis revealed that GPC-3 was an independent risk factor for 5-year survival rate （P=0.031） and disease-free survival rate （P=0.047）, together with tumor differentiation, Milan criteria and pre-operative alpha-fetoprotein.CONCLUSION： GPC-3 is a potential biomarker for poor prognosis after LT in HCC patients with HBV-associated cirrhosis.展开更多
Glypican-3 （GPC3） is reported as a great promising tumor marker for hepatocellular carcinoma （HCC） diagnosis. Highly sensitive and accurate analysis of serum GPC3 （sGPC3）, in combination with or instead of tradi...Glypican-3 （GPC3） is reported as a great promising tumor marker for hepatocellular carcinoma （HCC） diagnosis. Highly sensitive and accurate analysis of serum GPC3 （sGPC3）, in combination with or instead of traditional HCC marker alpha-fetoprotein （AFP）, is essential for early diagnosis of I-ICC. Biomaterial-functionalized magnetic particles have been utilized as solid supports with good biological compatibility for sensitive immunoassay. Here, the magnetic nanoparticles （MnPs） and magnetic microparticles （MmPs） with carboxyl groups were further modified with streptavidin, and applied for the development of chemiluminescence enzyme immunoassay （CLEIA）. After comparing between MnPs- and MmPs-based CLEIA, MnPs-based CLEIA was proved to be a better method with less assay time, greater sensitivity, better linearity and longer chemiluminescence platform. MnPs-based CLEIA was applied for detection of sGPC3 in normal liver, hepatocirrhosis, secondary liver cancer and HCC serum samples. The results indicated that sGPC3 was effective in diagnosis of HCC with high performance.展开更多
基金Supported by State Key Project Specialized for Infectious Diseases, No 2008ZX10002-015Beijing Municipal Health Bureau Key Project for Capital Medical Development, No 2007-1021
文摘AIM:To evaluate the diagnostic value of glypican-3(GPC3) in serum and liver for primary hepatocellular carcinoma(HCC).METHODS:Serum levels of GPC3 and α-fetoprotein(AFP) were measured in 75 patients with primary HCC and 32 patients with liver cirrhosis.Expression of GPC3 and AFP in 58 HCC and 12 cirrhotic specimens was detected with immunohistochemical staining.RESULTS:When the cut-off value of serum GPC3 was set at 300 ng/L,its sensitivity and specificity for HCC were 47.0% and 93.5%,respectively.Among the 14 patients with HCC at stage according to the Barcelona Clinic Liver Cancer staging system,the serum GPC3 level was higher than 300 ng/L in 50%(7/14) patients,the serum AFP level was not ≥ 400 μg/L in any patient.Combined serum AFP and GPC3 significantly increased the sensitivity to the diagnosis of HCC.The GPC3 expression was detected in cytoplasm of HCC cells but not in hepatocytes and bile ducts of benign tumors.Among the 58 HCC patients,the GPC3 was expressed in 100%(28/28) patients with their serum AFP level ≥ 400 μg/L,and in 90%(27/30) patients with their AFP level < 400 μg/L,respectively.The GPC3 was weakly or negatively expressed in all paracarcinomatous and cirrhotic tissue samples.AFP positive HCC cells were only found in 1 out of the 58 HCC patients.CONCLUSION:GPC3 protein is a sensitive and specific serum marker for diagnosis of early HCC.Its expression in liver tissues can be used to discriminate tumor cells from benign hepatic cells.
基金supported by grants-in-aid from the Projects of Medical Science (H200925)the Natural Science Foundation of Jiangsu Province,China (BK2008187)
文摘BACKGROUND:Hepatocellular carcinoma (HCC) is characterized by a multi-cause,multi-stage and multi-focus process of tumor progression.Its prognosis is poor and early diagnosis is of utmost importance.This study was undertaken to investigate the dynamic expression of oncofetal antigen glypican-3 (GPC-3) and GPC-3 mRNA in hepatocarcinogenesis and to explore their early diagnostic value for HCC.METHODS:A hepatoma model was induced in male Sprague-Dawley rats with 0.05% 2-fluorenylacetamide and confirmed by hematoxylin and eosin staining and gamma-glutamyltransferase (GGT) expression.Total RNA was purified and transcribed into cDNA by reverse transcription.Fragments of the GPC-3 gene were amplified by nested RT-PCR,and confirmed by sequencing.GPC-3 was analyzed by immunohistochemistry,Western blotting or ELISA.RESULTS:Positive GPC-3 expression showed as brown granule-like staining localized in the cytoplasm.Histological examination of hepatocytes revealed three morphological stages of granule-like degeneration,atypical hyperplasia (precancerous),and cancer formation,with a progressive increase of liver total RNA and GGT expression.The incidence of liver GPC-3 mRNA and GPC-3,and serum GPC-3 was 100%,100% and 77.8% in the HCC group,100%,100%,and 66.7% in the precancerous group,83.3%,83.3%,and 38.9% in the degeneration group,and no expression in the liver or blood of the control group,respectively.There was a positive correlation between liver GPC-3 mRNA and total RNA level (r=0.475,P<0.05) or liver GPC-3 (r=1.0,P<0.001) or serum GPC-3 (r= 0.994,P<0.001).CONCLUSION:Abnormal oncofetal antigen GPC-3 and GPC-3 mRNA expression in hepatocarcinogenesis may be promising molecular markers for early diagnosis of HCC.
基金Supported by Collaborative Research Fund from Chugai Pharmaceutical Co. (to Kataoka H)Grant-in-Aid from The Ministry of Education, Culuture, Sports, Science and Technology, Japan, No. 24390099 (to Kataoka H)
文摘Glypican-3(GPC3)is a cell surface oncofetal proteoglycan that is anchored by glycosylphosphatidylinositol.Whereas GPC3 is abundant in fetal liver,its expression is hardly detectable in adult liver.Importantly,GPC3is overexpressed in hepatocellular carcinoma(HCC),and several immunohistochemical studies reported that overexpression predicts a poorer prognosis for HCC patients.Therefore,GPC3 would serve as a useful molecular marker for HCC diagnosis and also as a target for therapeutic intervention in HCC.Indeed,some immunotherapy protocols targeting GPC3 are under investigations;those include humanized anti-GPC3cytotoxic antibody,peptide vaccine and immunotoxin therapies.When considering the clinical requirements for GPC3-targeting therapy,companion diagnostics to select the appropriate HCC patients are critical,and both immunohistochemical analysis of tissue sections and measurement of serum GPC3 level have been suggested for this purpose.This review summarizes current knowledge regarding the clinical implication of GPC3detection and targeting in the management of patients with HCC.
基金Supported by Grants-in-Aid for Scientific Research from the Ministry of Education,Culture,Sports,Science and Technology of Japan(to Yamamoto H,Imai K and Shinomura Y)Grants-in-Aid for Cancer Research from the Ministry of Health,Labor and Welfare of Japan(to Yamamoto H)
文摘AIM:To clarify the association of glypican-3(GPC3)expression with Wnt and other growth signaling molecules in hepatocellular carcinoma(HCC). METHODS:Expression of GPC3,Wnt,matrix metalloproteinases(MMPs),sulfatase(SULF)1,SULF2,and other growth signaling molecules was analyzed in HCC cell lines and tissue samples by real-time reverse transcriptionpolymerase chain reaction,immunoblotting,and/or immunostaining.Expression of various genes in GPC3 siRNA-transfected HCC cells was analyzed. RESULTS:GPC3 was overexpressed in most HCCs at mRNA and protein levels and its serum levels weresignificantly higher in patients with HCC than in non- HCC subjects(P<0.05).Altered expressions of various MMPs and growth signaling molecules,some of which were correlated with GPC3 expression,were observed in HCCs.Down-regulation of GPC3 expression by siRNA in GPC3-overexpressing HCC cell lines resulted in a significant decrease in expressions of MMP2,MMP14,fibroblast growth factor receptor 1,insulin-like growth factor 1 receptor.GPC3 expression was significantly correlated with nuclear/cytoplasmic localization ofβ-catenin. CONCLUSION:These results suggest that GPC3,in conjunction with MMPs and growth signaling molecules, might play an important role in the progression of HCC.
基金supported in part by grants-in-Aid from the Projects of Jiangsu Medical Science (HK201102, H200925)the Priority Academic Program Development of Jiangsu Higher Education Institution (PAPD)the Program of Nantong Society Undertaking and Technological Innovation (HS2011012),China
文摘BACKGROUND: The prognosis of hepatocellular carcinoma (HCC) is poor and its early diagnosis is of the utmost importance. This study aimed to investigate the values of glypican-3 (GPC-3) expression in the liver and sera and its gene transcription for diagnosis and monitoring of metastasis of HCC. METHODS: Liver GPC-3 was analyzed in HCC tissues from 36 patients by immunohistochemistry and Western blotting. GPC-3 mRNA from circulating peripheral blood mononuclear cells from 123 HCC patients or 246 patients with other diseases or 36 HCC tissues was amplified by RT-PCR, quantitative realtime PCR, and confirmed by DNA sequencing. Circulating GPC-3 level was detected by ELISA. RESULTS: The increasing expression of GPC-3 was observed from non-cancerous to cancerous tissues, with brown granule-like staining localized in tumor parts of atypical hyperplasia and HCC formation. The positive rate of GPC-3 was 80.6% in HCC, 41.7% in their paracancerous tissues, and none in distal cancerous tissues (P【0.001), with no significant difference in differentiation grade and tumor number except for size (Z=2.941, P=0.003). Serum GPC-3 was detected only in HCC (52.8%) and significant difference was found between GPC-3 and tumor size (χ2 =6.318, P=0.012) or HBV infection (χ2 =23.362, P【0.001). Circulating GPC-3 mRNA was detected in 70.7% of HCC tissues, with relation to TNM stage, periportal cancerous embolus, and extra-hepatic metastasis (P【0.001). The combination ofcirculating GPC-3, GPC-3 mRNA and alpha-fetoprotein is of complementary value for HCC diagnosis (94.3%). CONCLUSION: Both GPC-3 overexpression and GPC-3 mRNA abnormality could be used as markers for the diagnosis of HCC and monitoring its metastasis.
基金supported by the National High Technology Research and Development Program of China (2012AA020205)the Union Program of the Education Ministry,Guangdong Province (2011A090200028)the Combination Project of the Education Ministry,Guangdong Province (2010B090400422)
文摘Glypican-3(GPC3) is a promising tumor marker for hepatocellular carcinoma(HCC) diagnosis with high sensitivity and specificity.The aim of this study was to establish an immunohistochemical detection method for GPC3 using the 7D11 monoclonal antibody(7D11 mAb) and evaluate its application for HCC diagnosis.The feasibility of the 7D11 mAb was evaluated by immunohistochemistry performed on adjacent normal liver and intrahepatic cholangiocarcinoma(ICC) samples,Furthermore,the serum GPC3 levels were evaluated in 40 HCC patients,7 ICC patients and 50 healthy donors.The results showed that GPC3 was expressed in 85% of HCC tissues(34/40),but was undetectable in ICC tissues and adjacent normal tissues.GPC3 was significantly increased in the serum of HCC patients(17/40,42.5%) but was undetectable in the serum of ICC patients(0/7,0%) and healthy donors(0/50,0%).This prospective study evaluated the clinical usefulness of 7D11 mAb for GPC3 detection in HCC patients.In conclusion,the use of 7D11 mAb might be good for GPC3 large-scale applications for clinical diagnosis of HCC.
基金Supported by Tianjin Municipal Health Bureau Key Project for Key Laboratory for Critical Care Medicine Development
文摘AIM:To investigate the diagnostic value of glypican-3(GPC3) and its relationship with hepatocellular carcinoma(HCC) recurrence after liver transplantation.METHODS:HCC tissue samples(n = 31) obtained from patients who had undergone liver transplantation were analyzed.GPC3 mRNA and protein expression were analyzed by TaqMan real-time reverse transcription-polymerase chain reaction and immunohistochemistry.Correlation between the GPC3 expression and clinicopathological features was analyzed.The potential prognostic value of GPC3 was investigated by comparing recurrence-free survival between HCC patients with and without GPC3 expression.RESULTS:Using a cutoff value of 3.5 × 10-2,20 of 31 cancerous tissues had expression values of > 3.5 × 10-2,whereas 3 of 31 adjacent non-neoplastic parenchyma and 0 of 20 control liver tissues had expression values of > 3.5 × 10-2(P < 0.001).GPC3 protein was immunoexpressed in 68% of cancerous tissues,but not in adjacent non-neoplastic parenchyma and control liver tissues.Vascular invasion was significantly related to GPC3 expression(P < 0.05).Recurrence-free survival was significantly longer for patients without GPC3 mRNA overexpression(> 3.5 × 10-2) and those without vascular invasion(P < 0.05 for both).CONCLUSION:GPC3 expression may serve as a valuable diagnostic marker for HCC.GPC3 mRNA overexpression may be an adverse indicator for HCC patients after liver transplantation.
文摘AIM: To investigate the prognostic and clinicopathological significance of glypican-3 (GPC3) overexpression in hepatocellular carcinoma (HCC). METHODS: Publications were searched using PubMed, EMBASE, the Cochrane Library and the Chinese Biomedical Literature Database up to March 2013. Inclusion and exclusion criteria were established to screen eligible studies for meta-analysis. The hazard ratios (HRs) of the eligible studies were pooled using RevMan 5.2 software to evaluate the impact of GPC3 overexpression on overall survival (OS) and disease-free survival (DFS) in HCC patients. The correlation between GPC3 expression and clinicopathological parameters of HCC was also analyzed. RESULTS: A total of five studies with 493 patients were included in the meta-analysis. The combined HRs indicated that GPC3 overexpression can predict poor OS (n = 362 in 3 studies, HR = 2.18, 95%CI: 1.47-3.24, Z = 3.86, P = 0.0001) and DFS (n = 325 in 3 studies, HR = 2.05, 95%CI: 1.43-2.93, Z = 3.94, P < 0.0001) in HCC patients without heterogeneity. Egger's and Begg's tests were applied to detect publication bias, and the results showed that there was no evidence of publication bias detected in the OS studies (the P value for Egger's test was 0.216) or DFS studies (the P value for Egger's test was 0.488). The combined odds ratios (ORs) suggested that GPC3 expression tends to be associated with tumor vascular invasion (OR = 2.74, 95%CI: 1.15-6.52, P = 0.02), hepatic cirrhosis (OR = 2.10, 95%CI: 1.31-3.36, P = 0.002), poor tumor differentiation (OR = 0.22, 95%CI: 0.13-0.40, P < 0.00001) and advanced TNM stage (OR = 0.31, 95%CI: 0.18-0.51, P < 0.00001). CONCLUSION: From this study, we conclude that GPC3 overexpression tends to be associated with a poor prognosis (poor OS or DFS) in HCC. (C) 2014 Baishideng Publishing Group Inc. All rights reserved.
基金supported in part by the grants from the Projects of Jiangsu Medical Science(2013-WSW-011,2014-YY-028 and HK201102)the Qinglan and PAPD of Jiangsu Higher Education+1 种基金the Nantong Undertaking and Technological Innovation(H2014078)the International S&T Cooperation Program(2013DFA32150)of China
文摘BACKGROUND： The carcinogenesis of hepatocellular car- cinoma （HCC） is a multi-factorial, multi-step and complex process. Early diagnosis and effective treatments are of utmost importance. This review summarized the recent studies of on- cofetal glypican-3 （GPC-3）, a membrane-associated heparan sulfate proteoglycan, in the diagnosis and treatment of HCC. DATA SOURCES： English-language reports published from Iune 2001 to September 2014 were searched from MEDLINE. The key words searched included： GPC-3, biomarker, target and HCC. The sensitivity, specificity, positive and negative predictive values were extracted, and the effect of GPC-3 tar- geted therapy on HCC was also evaluated. RESULTS： GPC-3 plays a crucial role in HCC cell prolifera- tion and metastasis. It mediates oncogenesis involving signal- ing pathways during hepatocyte malignant transformation. GPC-3 expression is increased in atypical hyperplasia and cancerous tissues. GPC-3 levels in HCC patients are related to HBV infection, TNM stage, periportal cancerous embolus, and extrahepatic metastasis. The diagnostic accuracy of the combination of serum GPC-3 and alpha-fetoprotein in HCC is up to 94.3%. Down-regulation of GPC-3 with specific siRNA or anti-GPC-3 antibody alters cell migration, metastasis and invasion behaviors. The nude mice xenograft tumor growth is inhibited by silencing GPC-3 gene transcription.CONCLUSION： Oncofetal GPC-3 is a highly specific biomark- er for the diagnosis of HCC and a promising target molecule for HCC gene therapy.
基金supported by grants from the Special Fund Research of the Ministry of Health(2010.201002015)Specialized Research Fund of the Ministry of Education(20110001110044)Beijing Key Laboratory Special Fund(Z141107004414042)
文摘BACKGROUND：Glypican-3（GPC-3）is frequently overexpressed in hepatocellular carcinoma（HCC）.Recent studies have shown that GPC-3 is a highly efficient diagnostic biomarker of HCC and an indicator of poor prognosis in HCC patients who have undergone hepatectomy.However,its prognostic value in patients with HBV-associated HCC after liver transplantation（LT）is not clear.The present study is to evaluate the prognostic value of GPC-3 in patients with HBV-associated HCC after LT.METHODS： A cohort of 104 HCC patients with HBV-associ- ated cirrhosis who had undergone LT at our hospital between 2002 and 2011 were enrolled in this study. Samples of HCC were taken from these patients. GPC-3 protein expression was detected in paraffin-embedded specimens using immunohis- tochemistry. All related clinical data were obtained from the China Liver Transplant Registry. The relationship between GPC-3 expression and clinicopathological parameters was analyzed. Univariate and multivariate Cox-regression analyses were used to identify risk factors for poor prognosis. RESULTS： GPC-3 was expressed in samples from 74 （71.2%） of the 104 patients. GPC-3 was expressed only in HCC cells. Positive staining was correlated with tumor size （P=0.004）, encapsulation （P=0.018）, pathological stage （P--0.027）, portal vein invasion （P=0.043）, tumor differentiation （P=0.002） and the Milan criteria （P=0.016）. The 5-year survival rate and dis- ease-free survival rate of patients with GPC-3-positive were lower than those （38.2% vs 75.4%, P〈0.001; 30.8% vs 69.7%, P=0.001） of patients with GPC-3-negative. Multivariate Coxregression analysis revealed that GPC-3 was an independent risk factor for 5-year survival rate （P=0.031） and disease-free survival rate （P=0.047）, together with tumor differentiation, Milan criteria and pre-operative alpha-fetoprotein.CONCLUSION： GPC-3 is a potential biomarker for poor prognosis after LT in HCC patients with HBV-associated cirrhosis.
基金supported by the National Basic Research Program of China (973 Program,No.2007CB714507)the National Natural Science Foundation of China (No.90813015)
文摘Glypican-3 （GPC3） is reported as a great promising tumor marker for hepatocellular carcinoma （HCC） diagnosis. Highly sensitive and accurate analysis of serum GPC3 （sGPC3）, in combination with or instead of traditional HCC marker alpha-fetoprotein （AFP）, is essential for early diagnosis of I-ICC. Biomaterial-functionalized magnetic particles have been utilized as solid supports with good biological compatibility for sensitive immunoassay. Here, the magnetic nanoparticles （MnPs） and magnetic microparticles （MmPs） with carboxyl groups were further modified with streptavidin, and applied for the development of chemiluminescence enzyme immunoassay （CLEIA）. After comparing between MnPs- and MmPs-based CLEIA, MnPs-based CLEIA was proved to be a better method with less assay time, greater sensitivity, better linearity and longer chemiluminescence platform. MnPs-based CLEIA was applied for detection of sGPC3 in normal liver, hepatocirrhosis, secondary liver cancer and HCC serum samples. The results indicated that sGPC3 was effective in diagnosis of HCC with high performance.
