Value Of Glypican-3 Research Articles

Value of Glypican-3 as a Diagnostic and Prognostic Biomarker for Hepatocellular Carcinoma before and after Treatment. A Prospective Study

Abstract Background Hepatocellular carcinoma is a highly prevalent tumor globally and the world's second leading cause of cancer-related deaths. Glypican-3, a heparan sulfate proteoglycan expressed on the surface of HCC cells, has emerged as a new molecule with a strong link to occurrence and progression of HCC. This study was done to determine the role of Glypican-3 in diagnosis of HCC and its prognostic value following different treatment modalities. The study included thirty patients with liver cirrhosis and HCC on top, and thirty patients with liver cirrhosis without HCC, standard laboratory investigations, abdominal ultrasound and triphasic computed tomography were done for all patients. serum Alpha fetoprotein and Glypican-3 were measured in all patients before and one month after different treatment modalities Results Glypican-3 was significantly higher in HCC group (2.28 ± 0.97) in comparison to cirrhosis group (0.56 ± 0.31) with P-value 0.000. Glypican-3 level was higher in larger sized lesions with p value 0.023, one month after treatment with different modalities, Glypican-3 declined significantly (from 2.28 ± 0.97 to 1.44 ± 0.93) with p value 0.000. At a Cut-off point of > 1.1 ng/ml Glypican-3 has 93.3% sensitivity, 96.67% specificity, 96.6% PPV and 93.5% NPV for detection of HCC. Conclusion Glypican-3 can be a valuable diagnostic marker for HCC diagnosis and prognosis after various treatment modalities. And may be complementary to Alpha fetoprotein increasing overall sensitivity of HCC detection.

Value of Glypican-3 as a Diagnostic and Prognostic Biomarker for Hepatocellular Carcinoma before and after Treatment. A Prospective Study

Background: Hepatocellular carcinoma is a highly prevalent tumor globally and the world's second leading cause of cancer-related deaths. Glypican-3, a heparan sulfate proteoglycan expressed on the surface of HCC cells, has emerged as a new molecule with a strong link to occurrence and progression of HCC. Objective: This study was done to determine the role of Glypican-3 in diagnosis of HCC and its prognostic value following different treatment modalities. Patients and methods: The study included thirty patients with liver cirrhosis and HCC on top, and thirty patients with liver cirrhosis without HCC. Standard laboratory investigations, abdominal ultrasound and triphasic computed tomography were done for all patients. Serum alpha fetoprotein and Glypican-3 were measured in all patients before and one month after different treatment modalities. Results: Glypican-3 was significantly higher in HCC group (2.28 ± 0.97) in comparison to cirrhosis group (0.56 ± 0.31) with P-value 1.1 ng/ml Glypican-3 has 93.3% sensitivity, 96.67% specificity, 96.6% PPV and 93.5% NPV for detection of HCC. Conclusion: Glypican-3 can be a valuable diagnostic marker for HCC diagnosis and prognosis after various treatment modalities and may be complementary to alpha fetoprotein increasing overall sensitivity of HCC detection.

The Value of GPC3 and GP73 in Clinical Diagnosis of Hepatocellular Carcinoma.

The incidence of hepatocellular carcinoma (HCC) has increased over the past decades in China. Current screening methods of HCC such as detection of α-fetoprotein (AFP) combined with liver ultrasonography remain unsatisfactory. Many HCC patients have already missed the optimal treatment period when diagnosed. Our study aimed to evaluate the value of Glypican 3 (GPC3) and Golgi protein 73 (GP73) in the detection of HCC. Thirty-nine patients with HCC and 31 patients with liver cirrhosis were enrolled. The level of serum GPC3 and GP73 were determined by ELISA. The expression of GPC3 mRNA and GP73 mRNA in peripheral blood mononuclear cell (PBMC) and liver tissues were also measured with qRT-PCR. Then, receiving operating characteristic (ROC) curves were plotted to detect the sensitivity and specificity of serum GPC3 and GP73 in the diagnosis of HCC. The levels of serum GPC3 and GP73 in the HCC group were significantly higher than in the cirrhosis group (p < 0.0001). Patients with GPC3 > 9.3 μg/L and GP73 > 77.68 ng/mL had a risk of HCC of 92.31%. The HCC diagnosis ROC curve analysis indicated that when setting the GPC3 cutoff value > 9.3 μg/L, AUC = 0.956. The sensitivity and specificity of GPC3 were 89.74% and 96.77%, respectively, with a positive predictive value of 97.2%, negative predictive value of 88.2%, + LR of 27.82 and - LR of 0.11. When setting GP73 cutoff value > 77.68 ng/mL, AUC = 0.937. The sensitivity and specificity of GP73 were 92.31% and 83.87%, respectively, with positive predictive value of 87.8%, negative predictive value of 89.7%, + LR of 5.72 and - LR of 0.092. No significant difference (p > 0.05) was found between GPC3 and GP73 AUC in ROC curves, indicating that these two biomarkers were equivalent in the prediction of HCC. The expression of serum GPC3 and GP73 was significantly higher in the HCC patients compared with the cirrhosis patients. GPC3 and GP73 might be effective non-invasive diagnostic indicators of HCC.

Abstract 573: Glypican-3 is a predictive marker for recurrence of hepatocellular carcinoma after surgical resection, especially in early stage

Abstract Background and Objective: Even in early stages, recurrence risk of hepatocellular carcinoma (HCC) is high. Glypican-3 (GPC3) is specifically overexpressed in HCC, and its overexpression is correlated with poor prognosis in patients with HCC. Recent studies have shown the utility of GPC3 as a serum and immunohistochemical marker for the diagnosis of HCC. However, the diagnostic value of GPC3 as a predictive marker for recurrence of early-stage HCC is not well understood. Thus, in the present study, we evaluated the usefulness of GPC3 as a predictive marker for recurrence after surgical resection, especially in early-stage HCC. Methods: Plasma samples were collected from 27 patients with stageI HCC who underwent for surgical resection during May 2008 to October 2010. GPC3-expression of surgical specimens was analyzed by immunohistochemical staining. The novel anti-GPC3 mouse monoclonal antibodies were generated and the sandwich enzyme-linked immunosorbent assay (ELISA) system for detection of plasma GPC3 levels was established. Plasma GPC3 concentrations were measured by the developed novel sandwich ELISA system. Plasma samples of age-matched 39 non-liver disease patients were used as control. Results: During follow-up period (median, 738 days), recurrence was observed in 14 cases after surgical resection (51.8%). GPC3 positive rate by the immunohistochemical staining of resected specimen was 53% (13/23). There was a tendency towards a shorter recurrence-free survival (RFS) in GPC3 positive cases than in GPC3 negative cases (p = 0.233). The mean ± standard deviation (SD) of plasma GPC3 concentrations in control subjects was 110.12 ± 37.70 ng/ml, and cut-off value was determined to be 132 ng/ml (mean + 1.5 SD). In stageI HCC, the sensitivity and specificity were 40.7% and 92%, respectively. In the recurrence group, pre-operation plasma GPC3 levels were significantly higher than in the non-recurrence group(median, 191.7 ng/ml vs 29.7 ng/ml, p = 0.029). There was a tendency of shorter RFS in the pre-operation plasma GPC3 positive patients group compared with the negative group (median RFS, 16 months vs not reached), although this difference was not significant (p = 0.127). Among 11 cases remained recurrence-free for over 4 years of follow-up, pre-operation plasma GPC3 positive was only one case. The recurrence rate of patients with post-operation plasma GPC3 positive was significantly higher than GPC3 negative patients (p = 0.033). Conclusions: We have developed a novel ELISA system for detecting plasma GPC3 levels and determined utility of GPC3 as diagnostic marker of HCC. This study suggests GPC3 expression and plasma GPC3 levels might help in identification of patients at high risk of recurrence of HCC after surgical resection, especially in early stage. Citation Format: Kazuya Ofuji, Keigo Saito, Yasunari Nakamoto, Tetsuya Nakatsura. Glypican-3 is a predictive marker for recurrence of hepatocellular carcinoma after surgical resection, especially in early stage. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 573. doi:10.1158/1538-7445.AM2015-573

GPC3 plus alpha fetoprotein versus alpha fetoprotein alone in the diagnosis of hepatocellular carcinoma : a meta-analysis

Objective To investigate the diagnostic value of serum glypican-3 (GPC3) combined with alpha-fetoprotein (AFP) versus alpha fetoprotein alone for hepatocellular carcinoma.Methods A comprehensive electronic search and additional manual tracking were performed to retrieve published studies addressing the diagnostic value of GPC3 combined with AFP compared with AFP alone for liver cancer.The retrieved literatures were screened and selected according to pre-determined inclusion and exclusion criteria.Data were extracted and analyzed using the software STATA12.0.Summary receiver operating characteristic curves were used to compare test performance of the two.Results Nineteen studies met the inclusion criteria and were included into this study.Heterogeneity existed among these studies,but it was not possibly caused by the threshold effect.Therefore,we used the random effect model for quantitative analysis.The pooled accuracy indicator,sensitivity and specificity were 0.61 and 0.93 for AFP alone,and 0.84 and 0.86 for GPC3 combined with AFP,respectively.The area under summary receiver operating characteristics curve and Q index were 0.81 and 0.75 for AFP alone,and 0.91 and 0.85 for GPC3 combined with AFP.Conclusious GPC3 combined with AFP significantly improved the diagnostic sensitivity,and its specificity remained at a high level (0.86),indicating that the combined use of GPC3 and AFP is helpful for screening and early diagnosis of liver cancer. Key words: Glypican-3 ; Alpha-fetoprotein; Tumor marker; Liver cancer; Meta-analysis