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Glypican-3 (GPC3) is an essential reference target for hepatocellular carcinoma detection, follow-up and prediction. Herein, a dual-signal electrochemical aptasensor based on reduced graphene oxide-cuprous oxide (RGO-Cu 2 O) nanozyme was developed for GPC3 detection. The RGO-Cu 2 O nanoenzyme displayed excellent electron transport effect, large specific surface area and outstanding peroxidase-like ability. The differential pulse voltammetry (DPV) signal of Cu 2 O oxidation fraction and the chronoamperometry (i-t) signal of H 2 O 2 decomposition catalyzed by RGO-Cu 2 O nanozyme were used as dual-signal detection. Under optimal conditions, the log-linear response ranges were 0.1 to 500.0 ng/mL with the limit of detection 0.064 ng/mL for DPV technique, and 0.1-50.0 ng/mL for i-t technique (detection limit of 0.0177 ng/mL). The electrochemical aptasensor has remarkably analytical performance with wide response range, low detection limit, excellent repeatability and specificity, good recovery in human serum samples. The two output signals of one sample achieve self-calibration of the results, effectively avoiding the occurrence of possible leakage and misdiagnosis of a single detection signal, suggesting that it will be a promising method in the early biomarker detection., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Glypican-3 (GPC3) is exclusively overexpressed in most Hepatocellular carcinoma (HCC) tissue but not in normal liver tissue, making it a promising biomarker for the precise detection of HCC. In this paper, a label-free light-addressable potentiometric sensor (LAPS) decorated by platinumpalladium-hemin-reduced graphene oxide nanocomposites (PtPd@H-rGO NCs) was constructed for determination of GPC3. The GPC3 aptamer (GPC3 Apt ) and PtPd@H-rGO NCs were modified on the surface of silicon-based LAPS chip to build sensitive unit of LAPS system. A readout photocurrent elicited from a modulated light source, registers the localized surface potential change. When a bias voltage is provided to the LAPS system, the GPC3-GPC3 Apt complexes formed by the specific reaction between GPC3 and GPC3 Apt at the sensing interface can cause the sensitive membrane surface potential to change, resulting in the photocurrent-voltage (I-V) curves generate a corresponding offset response. Therefore GPC3 concentration can be determined by monitoring the potential shifts (△V). Under optimal conditions, the potential shift is linearly related to the concentration of GPC3 in the range of 0.001-3.00 μg/mL with the limit of detection (LOD) of 0.0001 μg/mL. The LAPS has a good analytical performance with good specificity, reproducibility and stability, and can be used for the detection of GPC3 in actual serum samples, which provides a broad application prospect for the combined application of LAPS and aptamers in biooassay., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Glypican-3 (GPC3) is a highly specific tumor marker for hepatocellular carcinoma (HCC), and plays an important role in reflecting the existence, therapeutic evaluation, monitoring and prognosis of HCC. Herein, an electrochemical aptasensor was designed for GPC3 detection with the reduced graphene oxide-hemin nanocomposites (RGO-Hemin) modified on the screen-printed electrode surface as the sensing platform and GPC3 aptamer as recognize molecule. In the existence of GPC3, the aptamer can specifically bind with the target GPC3 and form GPC3-aptamer conjugations on the sensing surface, which would increase the resistance of the electron transfer on the electrode and make the decrease of electrochemical signals of Hemin in RGO-Hemin nanocomposites. The electrochemical current change was recorded by differential pulse voltammetry (DPV). Scanning electron microscopy (SEM), Raman microscope (RM), cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) were used to characterize the GPC3 electrochemical aptasensor. Under the optimum conditions, the current response of the electrochemical aptasensor is linearly correlated with the concentration of GPC3 (0.001-10.0 μg/mL) with the detection limit of 2.86 ng/mL (S/N = 3) and the sensitivity of 0.134 μA/μM/cm 2 . In addition, the aptasensor was applied to the determination of GPC3 in spiked human plasma and the recoveries fluctuated from 102.68% to 117.29%. All these results show that the aptasensor has good specificity, sensitivity, stability and reproducibility for GPC3 detection., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships in this work., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Immunogenicity of immature pluripotent stem cells is a topic of intense debate. Immunogenic antigens, which are specific in pluripotent states, have not been described previously. In this study, we identified glypican-3 (GPC3), a known carcinoembryonic antigen, as a pluripotent state-specific immunogenic antigen. Additionally, we validated the applicability of human leukocyte antigen (HLA)-class I-restricted GPC3-reactive cytotoxic T lymphocytes (CTLs) in the removal of undifferentiated pluripotent stem cells (PSCs) from human induced pluripotent stem cell (hiPSC)-derivatives. HiPSCs uniquely express GPC3 in pluripotent states and were rejected by GPC3-reactive CTLs, which were sensitized with HLA-class I-restricted GPC3 peptides. Furthermore, GPC3-reactive CTLs selectively removed undifferentiated PSCs from hiPSC-derivatives in vitro and inhibited tumor formation in vivo. Our results demonstrate that GPC3 works as a pluripotent state-specific immunogenic antigen in hiPSCs and is applicable to regenerative medicine as a method of removing undifferentiated PSCs, which are the main cause of tumor formation., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Glypican-3 (GPC3) might be used as new biomarker of liver cancer for the development of new diagnostic methods. The most commonly used methods for protein detection are based on natural enzymes, which are easily affected by environmental conditions and suffer from the rigorous preparation conditions. Thus, the development of new enzyme mimetics with high and stable catalytic activity is of great significance in diagnostic applications. In this paper, copper ions (Cu 2+ ) was found to possess the peroxidase-like catalytic activity, which can catalyze H 2 O 2 -mediated oxidation of peroxidase substrate and obtain the oxidation product with color change. This catalytic activity is much more stable than other nanomaterials based peroxidase mimetics, and can significantly increase by increasing the concentration of H 2 O 2 . It is worth mentioning that the absorbance signal induced by 5 nM Cu 2+ can be easily detected. This Cu 2+ -catalyzed reaction can be also applied in the detection of GPC3 by using the anti-GPC3 antibody functionalized CuO NPs, which can release the Cu 2+ by dissolved in HCl solution. This method permits detection of as low as 0.26 pg mL -1 GPC3. This sensitivity is about one or several magnitudes higher than that of ELISA or other peroxidase mimetics based methods. The high catalytic activity of Cu 2+ and the signal amplification process of CuO NPs into high amount of Cu 2+ also make this method more simple and effective., (Copyright © 2016 Elsevier B.V. All rights reserved.)

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-associated 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 immunohistochemistry. 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 disease-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 Cox-regression 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.

Objective: The purpose of this study was to investigate the expression of glial cell derived neurotrophic factor (GDNF), glypican-1 (GPC-1), and matrix metalloproteinase-9 (MMP-9), and their association with clinicopathologic characteristics as well as prognostic significance in pancreatic cancer., Methods: Immunohistochemical assessment of GDNF, GPC-1, and MMP-9 was performed in 62 cases of surgically resected pancreatic cancer. Perineural invasion in pancreatic cancer was observed by marking nerve fiber with S-100, while 16 normal pancreatic tissues were used as normal control. Correlations of GDNF, GPC-1 and MMP-9 expressions with clinicopathologic parameters were analyzed. A survival analysis was performed to find the prognostic significance., Results: The expressions of GDNF, GPC-1 and MMP-9 in pancreatic cancer tissue were significantly higher than of those in normal pancreatic tissues (41/62 vs. 5/16 for GDNF, 35/62 vs. 2/16 for GPC-1, and 37/62 vs. 3/16 for MMP-9; p<0.01, respectively). The overexpression of GDNF, GPC-1, and MMP-9 in pancreatic cancer tissue was significantly related to the perineural invasion (p<0.05). Although the overexpression of these genes was related to poor survival, GPC-1 had an independent prognostic effect on overall survival., Conclusion: GPC-1 is significantly related to the perineural invasion of pancreatic cancer, holding some prognostic significance in patients with pancreatic cancer., (Copyright © 2012. Published by Elsevier B.V.)

Background/aims: Liver biopsy for hepatocellular carcinoma (HCC) detection is largely restricted to small hepatocellular lesions, which are often morphologically challenging, requiring careful distinction between dysplastic nodules (high-grade) and well-differentiated HCC., Methods: We investigated the diagnostic accuracy of a panel of markers (HSP70 GPC3 and GS), previously tested in resection specimens, in a series of liver biopsies of large regenerative nodules (n=13), low-grade dysplastic nodules (n=21), high-grade dysplastic nodules (n=50), very well-differentiated (VWD) (n=17), well-differentiated (WD-G1) (n=40) and G2-3 (n=35) HCC., Results: Almost all cases of large regenerative and low-grade dysplastic nodules did not stain while high-grade dysplastic nodules showed 1 marker (22%) but never 2 or 3. For HCC detection the overall accuracy of marker combination was 60.8% (3 markers) and 78.4% (2 markers) with 100% specificity. When restricted to VWD+WD-G1 HCC the accuracy was 57% (3 markers) and 72.9% (2 markers) with 100% specificity., Conclusions: This panel proved useful to detect well-differentiated HCC in biopsy. Two immunoreactive markers (out of 3) are recommended as the most valuable diagnostic combination for HCC detection. The diagnostic accuracy of the panel could be improved using additional markers, as suggested by studies of expression profiling in other human models.

Insulin stimulates glucose uptake in fat and muscle primarily by stimulating the translocation of vesicles containing facilitative glucose transporters, GLUT4, from intracellular compartments to the plasma membrane. Although cell surface externalization of GLUT4 is critical for glucose transport, the mechanism regulating cell surface GLUT4 remains unknown. Using a yeast two-hybrid screening system, we have screened GLUT4-binding proteins, and identified a novel glycosyl phosphatidyl inositol (GPI)-linked proteoglycan, Glypican3 (GPC3). We confirmed their interaction using immunoprecipitation and a GST pull-down assay. We also revealed that GPC3 and GLUT4 to co-localized at the plasma membrane, using immunofluorescent microscopy. Furthermore, we observed that glucose uptake in GPC3-overexpressing adipocytes was increased by 30% as compared to control cells. These findings suggest that GPC3 may play roles in glucose transport through GLUT4.

Hepatocellular carcinoma represents the fifth most frequent cancer in the world; it commonly occurs on cirrhotic liver. Prognosis and survival are still poor, mainly because of diagnosis at a late stage and/or recurrence of the disease. For this reason, surveillance strategies are widely used to screen for early occurrence of cancer in populations at risk. Alpha-foetoprotein is so far the only serological marker available, but its diagnostic accuracy is unsatisfactory because of low sensitivity despite reliable specificity. For this reason, new biomarkers for the diagnosis of hepatocellular carcinoma are in strong demand by clinicians. In this review, we will focus on new biomarkers currently under investigation, but also on still newer, very promising biomarkers that seem to significantly improve diagnosis.