• bioinformatics
• biomarker
• gene expression
• glypican-3
• lung adenocarcinoma

• Humans
• Male
• Glypicans/genetics
• Glypicans/metabolism
• Clinical Relevance
• Epigenesis, Genetic
• Neoplasm Recurrence, Local/genetics
• Adenocarcinoma of Lung/genetics
• Lung Neoplasms/pathology
• Prognosis

• T cells
• cell differentiation
• cell trafficking
• chemokines
• ex vivo imaging
• lymph nodes

• Adult
• Aged
• Carcinoma, Squamous Cell/metabolism
• Carcinoma, Squamous Cell/pathology
• Female
• Gene Expression Regulation, Neoplastic
• Gene Silencing
• Glypicans/biosynthesis
• Humans
• Male
• Middle Aged
• Mouth Neoplasms/metabolism
• Mouth Neoplasms/pathology
• Neoplasm Proteins/biosynthesis
• Wnt Signaling Pathway

Neoadjuvant chemoradiotherapy has been widely used in the treatment of locally advanced rectal cancer due to the excellent advantages of irradiation in cancer therapy. Unfortunately, not every patient can benefit from this treatment, therefore, it is of great significance to explore biomarkers that can predict irradiation sensitivity. In this study, we screened microRNAs (miRNAs) which were positively correlated with irradiation resistance and found that miRNA-552 and miRNA-183 families were positively correlated with the irradiation resistance of rectal cancer, and found that high expression of miRNA-96-5p enhanced the irradiation resistance of rectal cancer cells through direct regulation of the GPC3 gene and abnormal activation of the canonical Wnt signal transduction pathway. Based on the radioreactivity results of patient-derived xenograft models, this is the first screening report for radio-resistant biomarkers in rectal cancer. Our results suggest that miRNA-96-5p expression is an important factor affecting the radiation response of colorectal cancer cells.

• GPC3
• Wnt/β-catenin
• irradiation resistance
• miRNA-96-5p
• rectal cancer

Glypican 3 (GPC3) is a heparin sulphate proteoglycan whose expression is associated with several malignancies. However, its expression in non-small-cell lung carcinoma (NSCLC) is limited and ambiguous. This study aimed to comprehensively evaluate the expression of GPC3 in NSCLC and develop a risk-score model for predicting the prognosis of NSCLC.

The gene expression profiles of lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) were downloaded from the UCSC Xena database. Using the limma package, the differentially expressed genes (DEGs) between different comparison groups were analysed and the differential expression of GPC3 was calculated. A functional enrichment analysis was conducted for GPC3-associated genes using the DAVID tool. For the GPC3-associated genes shared by the four comparison groups, a protein–protein interaction network was built using the Cytoscape software. After conducting a survival analysis and a Cox regression analysis, the genes found to be significantly correlated with prognosis were selected to construct a risk-score model. Besides, the gene and protein levels of GPC3 were examined by quantitative reverse transcriptase-PCR (qRT-PCR) and immunohistochemistry (IHC) in LUSC tissues and paracancer tissues.

The differential expression of GPC3 was significant (adjusted P < 0.05) in the NSCLC vs. normal, LUAD vs. normal, LUSC versus normal, and LUAD versus. LUSC comparison groups. GPC3 directly interacted with SERPINA1, MFI2, and FOXM1. Moreover, GPC3 expression was significantly correlated with pathologic N, pathologic T, gender, and tumour stage in LUAD samples. Finally, the risk-score model (involving MFI2, FOXM1, and GPC3) for LUAD and that (involving SERPINA1 and FOXM1) for LUSC were established separately. The qRT-PCR result showed that GPC3 expression was much higher in the LUSC tissues than that in the normal group. The IHC results further showed that GPC3 is highly expressed in LUSC tissues, but low in paracancer tissues.

The three-gene risk-score model for LUAD and the two-gene risk-score model for LUSC might be valuable in improving the prognosis of these carcinomas.

• Differential expression analysis
• Glypican 3
• Lung adenocarcinoma
• Lung squamous cell carcinoma
• Protein–protein interaction network
• Risk-score model

• Biomarker
• DNA methylation
• Epigenetics
• Mesothelioma

Glypican-3 (GPC3) is a cell membrane glycoprotein that regulates cell growth and proliferation. Aberrant expression or distribution of GPC3 underlies developmental abnormalities and the development of solid tumours. The strongest evidence for the participation of GPC3 in carcinogenesis stems from studies on hepatocellular carcinoma and lung squamous cell carcinoma. To the best of our knowledge, the role of the GPC3 protein and its potential therapeutic application have never been studied in small cell lung carcinoma (SCLC), despite the known involvement of associated pathways and the high mortality caused by this disease. Therefore, the aim of the present study was to examine GPC3 targeting for SCLC immunotherapy. An immunotoxin carrying an anti-GPC3 antibody (hGC33) and Pseudomonas aeruginosa exotoxin A 38 (PE38) was generated. This hGC33-PE38 protein was overexpressed in E. coli and purified. ADP-ribosylation activity was tested in vitro against eukaryotic translation elongation factor 2. Cell internalisation ability was confirmed by confocal microscopy. Cytotoxicity was analysed by treating liver cancer (HepG2, SNU-398 and SNU-449) and lung cancer (NCI-H510A, NCI-H446, A549 and SK-MES1) cell lines with hGC33-PE38 and estimating viable cells number. A BrdU assay was employed to verify anti-proliferative activity of hGC33-PE38 on treated cells. Fluorescence-activated cell sorting was used for the detection of cell membrane-bound GPC3. The hGC33-PE38 immunotoxin displayed enzymatic activity comparable to native PE38. The protein was efficiently internalised by GPC3-positive cells. Moreover, hGC33-PE38 was cytotoxic to HepG2 cells but had no effect on known GPC3-negative cell lines. The H446 cells were sensitive to hGC33-PE38 (IC₅₀, 70.6±4.6 ng/ml), whereas H510A cells were resistant. Cell surface-bound GPC3 was abundant on the membranes of H446 cells, but absent on H510A. Altogether, the present findings suggested that GPC3 could be considered as a potential therapeutic target for SCLC immunotherapy.

• Wnt/β-catenin pathway
• glypican-3
• hepatocellular carcinoma
• immunotherapy
• immunotoxin
• small cell lung carcinoma

• cancer
• glycosylphosphatidylinositol
• glycosylphosphatidylinositol-anchored protein
• immunology
• immunotherapy

• biomarker
• cancer
• extracellular matrix
• glycosaminoglycan
• glypican
• heparan sulfate proteoglycan
• immunostaining

We previously reported the identification of monocarboxylate transporter 4 (MCT4) and glypican-3 (GPC3) as prognostic factors for hepatocellular carcinoma (HCC), which are now considered significant poor prognostic factors for the disease. This study aimed to clarify the detailed interaction of these two factors in HCC to improve our understanding of aggressive HCC phenotypes. A total of 225 Japanese patients with HCC from our previous study were subjected to immunohistochemical analyses.

The number of MCT4-positive (MCT4+) HCC cases was 47 (21%), and most MCT4+ HCC showed high GPC3 expression (94%, 44/47 cases). In 44 MCT4+/GPC3+ HCC cases, intratumoral heterogeneity of GPC3 or MCT4 expression was further evaluated. We observed reciprocal (inverse), synergistic, mixed reciprocal and synergistic, or irrelevant interaction of MCT4 and GPC3 expression in 29 (66%), 5 (11%), 1 (2%), and 9 cases (21%), respectively. The cases exhibiting reciprocal expression of both markers tended to have cirrhosis without a history of neoadjuvant therapy. In summary, although MCT4+ HCC cases are mostly GPC3+, intratumoral expression patterns of MCT4 and GPC3 are frequently reciprocal each other, suggesting that dual targeting of MCT4 and GPC3 may achieve a better antitumor effect for MCT4+ HCC cases.

• Glypican-3
• Hepatocellular carcinoma
• MCT4
• Monocarboxylic acid transporter

Recent studies suggest that glypican-1 (GPC-1) is a biomarker for prostate cancer, but there are few studies elucidating the role of GPC-1 in prostate cancer progression. We observed high expression of GPC-1 in more aggressive prostate cancer cell lines such as PC-3 and DU-145. While inhibition of GPC-1 expression in PC-3 cells decreased cell growth and migration in vitro, it surprisingly increased cell proliferation and migration in DU-145 cells, suggesting that the role of GPC-1 is cell type-dependent. Further, GPC-1 inhibition increased PC-3 tumor size in NCr nude mice xenografts. We hypothesized that the discrepancy between the in vitro and in vivo data is mediated by stromal cells in the tumor microenvironment. Thus, we tested the effect of tumor conditioned media (TCM) on gene expression in human mesenchymal stem cells and fibroblasts. Treatment of stromal cells with TCM from PC-3 cells transfected with GPC-1 shRNA increased the expression of migration markers, endocrine/paracrine biomolecules, and extracellular matrix components. Additionally, the decreased cell growth in GPC-1 knockdown PC-3 cells was rescued by coculturing with stromal cells. These data demonstrate the paradoxical role that GPC-1 plays in prostate cancer cell growth by interacting with stromal cells and through ECM remodeling and endocrine/paracrine signaling.

• GPC3
• lung squamous cell carcinoma
• proliferation
• tumorigenesis
• β-catenin

• Animals
• Apoptosis/genetics
• Carcinogenesis/genetics
• Carcinoma, Squamous Cell/genetics
• Carcinoma, Squamous Cell/pathology
• Cell Proliferation/genetics
• Female
• Gene Expression Regulation, Neoplastic/genetics
• Glypicans/genetics
• Heterografts
• Humans
• Liver Neoplasms/genetics
• Liver Neoplasms/pathology
• Male
• Mice
• Transcriptional Activation/genetics
• Wnt Signaling Pathway/genetics
• beta Catenin/genetics

• Cancer
• Cell signaling
• Drug development
• Glypicans
• Tumor microenvironment

• Autocrine and paracrine Wnt pathways
• Breast cancer dissemination
• Secreted GPC3
• Signaling network

• Autocrine Communication/genetics
• Breast Neoplasms/genetics
• Breast Neoplasms/metabolism
• Breast Neoplasms/pathology
• Cell Line, Tumor
• Cell Survival/genetics
• Disease Progression
• Female
• Gene Expression
• Glypicans/genetics
• Glypicans/metabolism
• Humans
• Paracrine Communication/genetics
• Protein Binding
• Proto-Oncogene Proteins c-akt/genetics
• Proto-Oncogene Proteins c-akt/metabolism
• Signal Transduction
• Wnt Signaling Pathway

• PICT 2013-1337 Préstamo BID FONCyT
• PIP 2013-112200120100100CO CONICET

• glypican-3
• invasion
• miR-96
• migration

Hepatocellular carcinoma (HCC) is one of the most deadly cancers worldwide. In patients with HCC, histopathogical differentiation is an important indicator of prognosis; however, because determination of HCC differentiation is difficult, the recently described immunohistochemical (IHC) marker glypican3 (GPC3) might assist in HCC prognostication.The goal of our study was to investigate GPC3's IHC staining pattern and define the relationship between its expression and patients' clinicopathologic features and overall survival. We retrieved clinical parameters from 101 pathologically diagnosed HCC patients' medical records and classified these patients into 4 clinical score categories (0–3) based on increasing GPC3 staining intensity and the percentage of stained tumor cells in their resection and biopsy specimens. Histopathological samples were well, moderately, and poorly differentiated in 33, 22, and 12 patients, respectively, and the GPC3 expression rate was 63%, 86%, and 92%,respectively. The median overall survival was 49.9 months (confidence interval (CI): 35.3–64.6 months) for clinical scores 0–1 and 30.7 months (CI: 19.4–41.9 months) for clinical scores 2–3. This difference was not statistically significant (P = .06) but showed a strong trend. In conclusion, a greater GPC3 expression is associated with a worse HCC prognosis and may be a promising prognostic marker.

• glypican-3
• hepatocellular carcinoma
• immunohistochemistry

Sulfonation is one of the most abundant cellular reactions modifying a wide range of xenobiotics as well as endogenous molecules which regulate important biological processes including blood clotting, formation of connective tissues, and functionality of secreted proteins, hormones, and signaling molecules. Sulfonation is ubiquitous in all tissues and widespread in nature (plants, animals, and microorganisms). Although sulfoconjugates were discovered over a century ago when, in 1875, Baumann isolated phenyl sulfate in the urine of a patient given phenol as an antiseptic, the significance of sulfonation and its roles in human diseases have been underappreciated until recent years. Here, we provide a current overview of the significance of sulfonation reactions in a variety of biological functions and medical conditions (with emphasis on cancer). We also discuss research areas that warrant further attention if we are to fully understand how deficiencies in sulfonation could impact human health which, in turn, could help define treatments to effect improvements in health.

• PAPSS
• heparan sulfate
• sulfonation
• sulfotransferases
• tyrosine sulfation

• breast cancer
• epithelial-mesenchymal transition
• glypican-3
• invasion
• metastasis

• Cancer
• Decorin
• Glycosaminoglycans
• Glypicans
• Perlecan
• Proteoglycans
• Serglycin
• Syndecans
• Versican

There are limited strategies for the treatment of hepatocellular carcinoma (HCC). In this study, we prepared a Bispecific T cell engager (BiTE) targeting Glypican 3 (GPC3) and CD3. The GPC3/CD3 BiTE was prepared by fusing the single-chain variable fragment (scFv) of the humanized anti-GPC3 antibody (9F2) with the scFv of the anti-CD3 antibody (OKT3). The in vitro and in vivo cytotoxic activities of the GPC3/CD3 BiTE were evaluated against various HCC cell lines. The GPC3/CD3 BiTE could efficiently mediate the T cell killing of GPC3-positive HCC in vitro, which was dependent on GPC3 expression on the surface of HCC cells. Moreover, our study indicates that, in the presence of the GPC3/CD3 BiTE, T cells could efficiently destroy GPC3-positive human HCC cells in vitro and in vivo. Additionally, our study further proved that GPC3 is not expressed in normal tissues. Thus, GPC3 may be a cancer-specific antigen. Collectively, these findings suggest that this anti-GPC3 BiTE might be a promising anti-tumor reagent for patients with GPC3-positive HCC.

• bispecific T cell engager
• glypican-3
• hepatocellular carcinoma
• immunotherapy

The connection between colorectal cancer (CRC) and Wnt signaling pathway activation is well known, but full elucidation of the underlying regulation of the Wnt/β-catenin pathway and its biological functions in CRC pathogenesis is still needed. Here, the azoxymethane/dextran sulfate sodium salt (AOM/DSS) murine model has been used as an experimental platform able to mimic human sporadic CRC development with predictable timing. We performed genome-wide expression profiling of AOM/DSS-induced tumors and normal colon mucosa to identify potential novel CRC biomarkers. Remarkably, the enhanced expression of Notum, a conserved feedback antagonist of Wnt, was observed in tumors along with alterations in Glypican-1 and Glypican-3 levels. These findings were confirmed in a set of human CRC samples. Here, we provide the first demonstration of significant changes in Notum and glypicans gene expression during CRC development and present evidence to suggest them as potential new biomarkers of CRC pathogenesis.

• Notum
• WNT-pathway
• colorectal carcinogenesis
• glypicans
• predictable animal models

Proteoglycans are a group of molecules that contain at least one glycosaminoglycan chain, such as a heparan, dermatan, chondroitin, or keratan sulfate, covalently attached to the protein core. These molecules are categorized based on their structure, localization, and function, and can be found in the extracellular matrix, on the cell surface, and in the cytoplasm. Cell-surface heparan sulfate proteoglycans, such as syndecans, are the primary type present in healthy liver tissue. However, deterioration of the liver results in overproduction of other proteoglycan types. The purpose of this article is to provide a current summary of the most relevant data implicating proteoglycans in the development and progression of human and experimental liver cancer. A review of our work and other studies in the literature indicate that deterioration of liver function is accompanied by an increase in the amount of chondroitin sulfate proteoglycans. The alteration of proteoglycan composition interferes with the physiologic function of the liver on several levels. This article details and discusses the roles of syndecan-1, glypicans, agrin, perlecan, collagen XVIII/endostatin, endocan, serglycin, decorin, biglycan, asporin, fibromodulin, lumican, and versican in liver function. Specifically, glypicans, agrin, and versican play significant roles in the development of liver cancer. Conversely, the presence of decorin could potentially provide protective effects.

• Cancer
• Cell regulation
• Heparan sulfate
• Liver
• Proteoglycans

• Agrin/metabolism
• Animals
• Carcinoma, Hepatocellular/etiology
• Carcinoma, Hepatocellular/metabolism
• Glycosaminoglycans/chemistry
• Glycosaminoglycans/metabolism
• Glypicans/metabolism
• Heparan Sulfate Proteoglycans/chemistry
• Heparan Sulfate Proteoglycans/metabolism
• Humans
• Liver Neoplasms/etiology
• Liver Neoplasms/metabolism
• Liver Neoplasms, Experimental/etiology
• Liver Neoplasms, Experimental/metabolism
• Proteoglycans/chemistry
• Proteoglycans/metabolism
• Syndecan-1/metabolism
• Versicans/metabolism

Tumour relapse is recognized to be the prime fatal burden in patients affected by head and neck squamous cell carcinoma (HNSCC), but no discrete molecular trait has yet been identified to make reliable early predictions of tumour recurrence. Expression of cell surface proteoglycans (PGs) is frequently altered in carcinomas and several of them are gradually emerging as key prognostic factors.

A PG expression analysis at both mRNA and protein level, was pursued on primary lesions derived from 173 HNSCC patients from whom full clinical history and 2 years post-surgical follow-up was accessible. Gene and protein expression data were correlated with clinical traits and previously proposed tumour relapse markers to stratify high-risk patient subgroups.

HNSCC lesions were indeed found to exhibit a widely aberrant PG expression pattern characterized by a variable expression of all PGs and a characteristic de novo transcription/translation of GPC2, GPC5 and NG2/CSPG4 respectively in 36%, 72% and 71% on 119 cases. Importantly, expression of NG2/CSPG4, on neoplastic cells and in the intralesional stroma (Hazard Ratio [HR], 6.76, p = 0.017) was strongly associated with loco-regional relapse, whereas stromal enrichment of SDC2 (HR, 7.652, p = 0.007) was independently tied to lymphnodal infiltration and disease-related death. Conversely, down-regulated SDC1 transcript (HR, 0.232, p = 0.013) uniquely correlated with formation of distant metastases. Altered expression of PGs significantly correlated with the above disease outcomes when either considered alone or in association with well-established predictors of poor prognosis (i.e. T classification, previous occurrence of precancerous lesions and lymphnodal metastasis). Combined alteration of all three PGs was found to be a reliable predictor of shorter survival.

An unprecedented PG-based prognostic portrait is unveiled that incisively diversifies disease course in HNSCC patients beyond the currently known clinical and molecular biomarkers.

The online version of this article (doi:10.1186/s12885-015-1336-4) contains supplementary material, which is available to authorized users.

• Breast cancer
• Decorin
• Glypicans
• Proteoglycans
• Serglycin
• Syndecans

• Golgi protein 73
• differential diagnosis
• glypican-3
• hepatocellular carcinoma
• α-fetoprotein

α-Fetoprotein (AFP) is the biomarker most widely used to detect hepatocellular carcinoma (HCC), despite its suboptimal diagnostic accuracy. Glypican-3 (GPC3) and osteopontin (OPN) are secreted glycoproteins that are reportedly associated with tumorigenesis and metastasis. This study was conducted to evaluate the clinical utility of using plasma GPC3 and OPN as diagnostic biomarkers for HCC.

We measured the plasma levels of GPC3 and OPN in 120 HCC and 40 chronic liver disease (CLD) patients via an enzyme-linked immunosorbent assay. The diagnostic accuracy of each tumor marker was evaluated using receiver operating characteristic (ROC) curve analysis.

The GPC3 levels in the HCC patients (75.8 ng/mL) were significantly higher (p=0.020) than the levels in patients with CLD (66.4 ng/mL). The area under the ROC curve (AUROC) values for GPC3 and OPN were 0.62 and 0.51, respectively. In subgroup analyses, including subgroups of HCC patients with low serum AFP and PIVKA II levels, the AUROC of GPC3 remained relatively high (0.66), and GPC3 showed a high sensitivity (62.1%) for detecting small HCC tumors.

The plasma levels of GPC3 and OPN demonstrated low diagnostic accuracy for HCC. However, GPC3 may have a complementary role in diagnosing HCC in patients with nondiagnostic levels of conventional tumor markers and with small-sized tumors.

• Glypican-3
• Hepatocellular carcinoma
• Osteopontin

• CD34
• GP73
• GPC3
• hepatocellular carcinoma
• immunohistochemistry

• Adenocarcinoma/metabolism
• Adenocarcinoma/pathology
• Adult
• Aged
• Aged, 80 and over
• Bile Duct Neoplasms/metabolism
• Bile Duct Neoplasms/pathology
• Bile Ducts, Intrahepatic/metabolism
• Bile Ducts, Intrahepatic/pathology
• Carcinoma, Hepatocellular/metabolism
• Carcinoma, Hepatocellular/pathology
• Carcinoma, Neuroendocrine/metabolism
• Carcinoma, Neuroendocrine/pathology
• Carcinoma, Squamous Cell/metabolism
• Carcinoma, Squamous Cell/pathology
• Cholangiocarcinoma/metabolism
• Cholangiocarcinoma/pathology
• Female
• Gastrointestinal Neoplasms/metabolism
• Gastrointestinal Neoplasms/pathology
• Glypicans/metabolism
• Humans
• Immunohistochemistry
• Male
• Middle Aged
• Pancreatic Neoplasms/metabolism
• Pancreatic Neoplasms/pathology

• proteoglycans
• tumor growth
• metastasis formation
• tumor marker
• immunotherapeutics

• Biomarkers, Tumor/metabolism
• Cell Transformation, Neoplastic
• Disease Progression
• Humans
• Immunotherapy
• Neoplasms/immunology
• Neoplasms/metabolism
• Neoplasms/pathology
• Proteoglycans/metabolism

• Child
• Child, Preschool
• Gene Expression Profiling
• Gene Expression Regulation, Neoplastic
• Humans
• Male
• Multiple Endocrine Neoplasia Type 1/genetics
• Multiple Endocrine Neoplasia Type 1/pathology
• Pituitary Neoplasms/genetics
• Pituitary Neoplasms/pathology

• Adult
• Aged
• Biomarkers, Tumor/genetics
• Biomarkers, Tumor/metabolism
• Blotting, Western
• Carcinoma, Squamous Cell/genetics
• Carcinoma, Squamous Cell/metabolism
• Carcinoma, Squamous Cell/pathology
• Female
• Follow-Up Studies
• Glypicans/genetics
• Glypicans/metabolism
• Humans
• Lung Neoplasms/genetics
• Lung Neoplasms/metabolism
• Lung Neoplasms/pathology
• Lymphatic Metastasis
• Male
• Middle Aged
• Neoplasm Staging
• Prognosis
• RNA, Messenger/genetics
• Real-Time Polymerase Chain Reaction
• Reverse Transcriptase Polymerase Chain Reaction

• perlecan
• endorepellin
• lg3
• vegf
• syndecan
• glypican
• heparanase
• small leucine-rich proteoglycans
• decorin
• lumican

• Animals
• Cell Proliferation
• Humans
• Neoplasms/blood supply
• Neoplasms/metabolism
• Neoplasms/pathology
• Neovascularization, Pathologic/metabolism
• Proteoglycans/metabolism
• Signal Transduction
• Tumor Microenvironment

• R01 CA138340 NCI NIH HHS
• CA135075 NCI NIH HHS
• R01 CA039481 NCI NIH HHS
• CA055819 NCI NIH HHS
• CA39481 NCI NIH HHS
• R01 CA047282 NCI NIH HHS
• R01 CA135075 NCI NIH HHS
• P01 CA055819 NCI NIH HHS
• CA47282 NCI NIH HHS
• CA120975 NCI NIH HHS
• R01 CA120975 NCI NIH HHS

AIM: To analyze the expression of glypican 3 (GPC3) in different liver diseases and to explore its significance in early diagnosis of hepatocellular carcinoma (HCC).

METHODS: The expression of GPC3 and α-fetoprotein (AFP) was detected by immunohistochemistry in 126 liver needle biopsy specimens from 13 patients with very early stage HCC, 44 patients with early stage HCC, 16 patients with dysplastic nodules, 29 patients with liver cirrhosis, and 24 patients with hepatitis, and in 57 resected HCC specimens from patients with intermediate and advanced HCC. Twenty-eight resected normal liver tissue specimens were used as controls.

RESULTS: The expression of GPC3 in HCC differed significantly from those in other liver diseases (all P < 0.01). Detection of GPC3 expression showed a higher diagnostic sensitivity (80.7%) and specificity (99.4%) than that of AFP (37.7% and 93.6%, respectively). GPC3 was expressed in 92.3% of very early stage HCC and in 72.7% of early stage of HCC. In contrast, AFP only appeared in 38.5% of very early stage HCC and in 34.1% of early stage HCC. The positive rates of GPC3 expression in very early and early stage HCC were significantly higher than those in dysplastic nodules (both P < 0.01). GPC3 and AFP expression was not detected in liver cirrhosis, hepatitis or normal liver tissue. In patients with small HCC, the positive rate of GPC3 expression was 78.6%, and combined detection of GPC3 and AFP had a sensitivity of 85.7%. In patients with small HCC who had an AFP of ≤20 μg/L, the positive rate of GPC3 expression was 70%. The recurrence rate after radical surgery in GPC3-positive patients was higher than that of GPC3-negative ones (P < 0.05).

CONCLUSION: GPC3 is highly expressed in HCC. Detection of GPC3 expression has a high sensitivity and specificity for diagnosis of very early and early stage HCC and therefore represents a potential diagnostic parameter for early HCC. Immunohistochemistry detection of GPC3 in liver needle biopsy specimens is an effective ancillary tool for early diagnosis of HCC. GPC3 expression is an independent prognostic factor for HCC recurrence after surgery.

• Hepatocellular carcinoma
• Glypican 3
• Differential diagnosis
• Live biopsy