Evaluating clinical and prognostic implications of Glypican-3 in hepatocellular carcinoma

Kaseb, Ahmed O.; Hassan, Manal M.; Laçin, Şahin; Abdel-Wahab, Reham; Amin, Hesham M.; Shalaby, Ahmed; Wolff, Robert A.; Yao, James C.; Rashid, Asif; Vennapusa, Bharathi; Feng, Janine; Ohtomo, Toshihiko

doi:10.18632/oncotarget.12066

Cited by 41 publications

(34 citation statements)

References 60 publications

(45 reference statements)

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“…This finding is consistent with previous reports (26,27). It has been reported that GPC3 is expressed in cancerous cells as well as non-cancerous surrounding cells, and that the prognosis of GPC3-positive HCC patients is poor (12,14,28,29). This may indicate that FL-GPC3 is produced by the tumor itself but as well as by precancerous lesions located in the surrounding liver tissue.…”

Section: Discussionsupporting

confidence: 93%

Usefulness of plasma full‑length glypican‑3 as a predictive marker of hepatocellular carcinoma recurrence after radial surgery

Miura

Fujinami²,

Shimizu³

et al. 2020

Oncol Lett

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Predicting the risk of hepatocellular carcinoma (HCC) recurrence before treatment is necessary for developing subsequent treatment policies. Several tumor markers found in blood, such as alpha-fetoprotein (AFP) and protein induced by vitamin K absence or antagonist-II (PIVKA-II), are presently used to determine the occurrence and recurrence of HCC and to predict patient prognosis. However, these markers are insufficient for these purposes as certain patients have HCC recurrence despite exhibiting negative AFP and PIVKA-II. The present study identified glypican-3 (GPC3), an embryonal carcinoma antigen that is expressed specifically in HCC and is secreted into blood. Although the N-terminal domain of GPC3 in sera may be a potential prognostic factor for HCC, its biological role remains unclear. By contrast, full-length GPC3 (FL-GPC3) is reported to serve important roles in cell differentiation, proliferation and signaling events that cause HCC. Given the biological roles of FL-GPC3 in HCC progression, the present study evaluated its potential as a predictive marker of HCC recurrence. In the present study, a novel measurement system was constructed to specifically measure plasma FL-GPC3. Subsequently, its ability to predict recurrence after radical surgery in 39 HCC patients was evaluated. The results revealed that preoperative FL-GPC3 levels in patients with recurrence were significantly higher than those in patients without recurrence, suggesting that FL-GPC3 could be a better predictive maker of risk of recurrence than AFP or PIVKA-II. Furthermore, it was determined that the combination of FL-GPC3, AFP and PIVKA-II could predict recurrence within one year of radical surgery with high sensitivity and specificity. Based on these results, the validation of FL-GPC3 as a predictive marker of HCC recurrence in a larger population is warranted.

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Section: Discussionsupporting

confidence: 93%

Usefulness of plasma full‑length glypican‑3 as a predictive marker of hepatocellular carcinoma recurrence after radial surgery

Miura

Fujinami²,

Shimizu³

et al. 2020

Oncol Lett

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“…Many studies have reported that GPC3 expression is correlated with a poor prognosis in HCC [ 38 , 39 ], and that GPC3 may be a prognostic marker for curative resection [ 40 , 41 , 42 ] and HCC recurrence following liver transplantation [ 43 ]. Two meta-analyses recently indicated that GPC3 overexpression was significantly associated with poor prognosis in patients with HCC [ 44 , 45 ].…”

Section: Cell Surface Proteoglycan (Glycosylphosphatidylinositol-amentioning

confidence: 99%

Proteoglycans Are Attractive Biomarkers and Therapeutic Targets in Hepatocellular Carcinoma

Tanaka

Tateishi

Koike

2018

IJMS

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Proteoglycans, which consist of a protein core and glycosaminoglycan chains, are major components of the extracellular matrix and play physiological roles in maintaining tissue homeostasis. In the carcinogenic tissue microenvironment, proteoglycan expression changes dramatically. Altered proteoglycan expression on tumor and stromal cells affects cancer cell signaling pathways, which alters growth, migration, and angiogenesis and could facilitate tumorigenesis. This dysregulation of proteoglycans has been implicated in the pathogenesis of diseases such as hepatocellular carcinoma (HCC) and the underlying mechanism has been studied extensively. This review summarizes the current knowledge of the roles of proteoglycans in the genesis and progression of HCC. It focuses on well-investigated proteoglycans such as serglycin, syndecan-1, glypican 3, agrin, collagen XVIII/endostatin, versican, and decorin, with particular emphasis on the potential of these factors as biomarkers and therapeutic targets in HCC regarding the future perspective of precision medicine toward the “cure of HCC”.

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“…Glypican-3 (GPC-3), a special marker of HCC, has been used to identify the HCC from other tumors and to evaluate the prognosis. GPC-3 is a member of the glypican family, which influences cell growth, differentiation, and migration [15]. GPC-3 is highly expressed in HCC, but not in cholangiocarcinoma or normal hepatic cells and is low express in well differential HCC [16,17].…”

Section: Backgroudmentioning

confidence: 99%

“…GPC-3 is highly expressed in HCC, but not in cholangiocarcinoma or normal hepatic cells and is low express in well differential HCC [16,17]. Previous studies have shown that higher GPC-3 expression level in HCC is a risk factor for shorter overall survival (OS) and levels of GPC-3 expression in poorly-differentiated tumor cells were higher than moderately-and well-differentiated HCC [15,18].…”

Section: Backgroudmentioning

confidence: 99%

Combined Texture Analysis of MR images and Glypican-3 to Identify the Differentiated Degree of Hepatocellular Carcinoma: a retrospective study

Feng¹,

Zhang²,

Liu³

et al. 2020

Preprint

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Abstract BACKGROUND To explore the clinical value of texture analysis of MR images (multiphase Gd-EOB-DTPA-enhanced MRI and T2 weighted imaging (T2WI) and the glypican-3 (GPC-3) to identify the differentiated degree of hepatocellular carcinoma (HCC). METHOD In this retrospective study, 104 participants were enrolled (GPC-3 data obtained in 51 participants). Each participant performed preoperative Gd-EOB-DTPA-enhanced MR scanning. Texture analysis was calculated by MaZda and then using the B11 program for data analysis and classification. The performance of texture features and GPC-3 in identifying the differentiated degree of HCC was assessed by receiver operating characteristic (ROC) analysis. RESULTS There were no statistically significances for the expression of GPC-3 between poorly-, well- and moderately-differentiated HCC. The area under the curve (AUC) of the combined texture features between poorly- and well-differentiated HCC, poorly- and moderately-differentiated HCC, moderately- and well-differentiated HCC was 0.812, 0.879 and 0.808 respectively. With GPC-3 combined, the AUC was increased to 0.868, while accuracy was decreased, in poorly- verse well-differentiated HCC, and the AUC and accuracy were the same as those without GPC-3 combined in poorly- verse moderately-differentiated HCC. Although the AUC was increased to 0.818 with GPC-3 combined in moderately- verse well-differentiated HCC, there were no statistical significance for the value change (p>0.05). CONCLUSION S Texture analysis of Gd-EOB-DTPA-enhanced MRI and T2WI are valuable in identifying the differentiated degree of HCC. There is no significant effect of GPC-3 in identifying the differentiated degree of HCC, suggesting the promising value of texture analysis of MR images in the precise presurgical diagnosis of HCC.

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Evaluating clinical and prognostic implications of Glypican-3 in hepatocellular carcinoma

Cited by 41 publications

References 60 publications

Usefulness of plasma full‑length glypican‑3 as a predictive marker of hepatocellular carcinoma recurrence after radial surgery

Usefulness of plasma full‑length glypican‑3 as a predictive marker of hepatocellular carcinoma recurrence after radial surgery

Proteoglycans Are Attractive Biomarkers and Therapeutic Targets in Hepatocellular Carcinoma

Combined Texture Analysis of MR images and Glypican-3 to Identify the Differentiated Degree of Hepatocellular Carcinoma: a retrospective study

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