• Hepatocellular carcinoma
• antibody conjugation, glypican 3
• chitosan
• drug delivery
• idarubicin
• nanobubbles

• Chitosan/chemistry
• Carcinoma, Hepatocellular/drug therapy
• Carcinoma, Hepatocellular/pathology
• Idarubicin/administration & dosage
• Idarubicin/pharmacology
• Animals
• Humans
• Liver Neoplasms/drug therapy
• Liver Neoplasms/pathology
• Mice
• Cell Line, Tumor
• Tissue Distribution
• Xenograft Model Antitumor Assays
• Mice, Nude
• Drug Carriers/chemistry
• Drug Delivery Systems
• Mice, Inbred BALB C
• Cell Survival/drug effects
• Nanoparticles/chemistry

• GPC-3
• Hepatocellular carcinoma
• Precision medicine
• Theranostic biomarker/molecular target

• Humans
• Glypicans/metabolism
• Carcinoma, Hepatocellular/diagnosis
• Carcinoma, Hepatocellular/metabolism
• Carcinoma, Hepatocellular/pathology
• Liver Neoplasms/metabolism
• Liver Neoplasms/diagnosis
• Liver Neoplasms/pathology
• Biomarkers, Tumor/metabolism
• Molecular Targeted Therapy/methods
• Animals

• biomarker
• early detection
• glypican-3
• hepatocellular carcinoma

• hepatocellular carcinoma
• immunotherapy
• signaling pathways
• targeted therapy

• National Nature Science Foundation of China

• fibrosis
• mesenchymal differentiation
• myofibroblasts
• stem cell pathology

• Rats
• Animals
• Histiocytoma, Malignant Fibrous/pathology
• Histiocytoma, Malignant Fibrous/veterinary
• Myofibroblasts
• Immunohistochemistry
• Endothelial Cells/pathology
• Stem Cells
• Fibrosis

• biomarker
• diagnosis
• hepatocellular carcinoma
• monitor
• optical aptasensor
• prognosis

• drug delivery
• glypican 3
• hepatocellular carcinoma
• nanomedicine
• polymeric nanoparticles
• targeted therapy

• Carcinoma, Hepatocellular/drug therapy
• Carcinoma, Hepatocellular/metabolism
• Drug Resistance
• Glypicans/metabolism
• Humans
• Liver Neoplasms/drug therapy
• Liver Neoplasms/metabolism
• Nanotechnology
• Therapies, Investigational

• NA Governo Italiano

• ALISA
• Aptablotting
• Aptaprobe
• Aptaprobe-based imaging
• Cancer diagnosis
• Glypican-3
• Hepatocellular carcinoma
• Structure-based molecular interaction

• Carcinoma, Hepatocellular/pathology
• Glypicans/metabolism
• Humans
• Liver Neoplasms/pathology

• NRF-2020R1A2C1009463 National Research Foundation of Korea
• 2020R1A6A1A06046235 National Research Foundation of Korea
• MAFRA_321108-04 Korea Institute of Planning and Evaluation for Technology in Food, Agriculture, Forestry and Fisheries

Yolk sac tumor (YST) is a germ cell tumor. It is primarily located in the gonads but can also occur extragonadally (extragonadal yolk sac tumor - EGYST), most commonly in the pelvis, retroperitoneum or mediastinum. Only a few YSTs of the urachus have been described.

We present a rare case report of a 37-year-old male with episodes of macroscopic hematuria. The histological specimen obtained by transurethral resection showed a solid, and in some parts papillary infiltrative, high-grade tumor with numerous areas of marked nuclear atypia and clear invasion between the detrusor bundles. Glandular pattern has been observed in only minority of the tumor. Immunohistochemistry showed significant positivity for GPC3, SALL4 and cytokeratins AE1/AE3, while KRT7 and GATA3 were negative. We concluded that the biopsy findings were consistent with urothelial carcinoma with infrequent YST differentiation. In definitive surgical specimens we found a malignant epithelial, glandular and cystically arranged tumor of germinal appearance arising from urachus. The surrounding urothelium was free of invasive or in situ tumor changes. We reclassified the tumor as a urachal YST.

EGYST was suspected because glandular and hepatoid structures were found, but the presence of these structures should be verified by immunohistochemistry.

• Extragonadal yolk sac tumor
• Urachal yolk sac tumor
• Yolk sac tumor

• Abdomen/diagnostic imaging
• Adult
• Bias
• Biomarkers, Tumor/blood
• Carcinoma, Hepatocellular/blood
• Carcinoma, Hepatocellular/diagnosis
• Carcinoma, Hepatocellular/pathology
• Case-Control Studies
• Chronic Disease
• Confidence Intervals
• Cross-Sectional Studies
• Female
• Humans
• Liver Diseases/complications
• Liver Neoplasms/blood
• Liver Neoplasms/diagnosis
• Liver Neoplasms/pathology
• Male
• Sensitivity and Specificity
• Ultrasonography/methods
• alpha-Fetoproteins/analysis

Distinguishing malignancy from healthy tissue is essential for oncologic surgery. Targeted imaging during an operation aids the surgeon to operate better. The present tracers for detecting cancer are directed against proteins that are overexpressed on the membrane of tumor cells. This review evaluates the use of tumor-associated sugar molecules as an alternative for proteins to image cancer tissue. These sugar molecules are present as glycans on glycosylated membrane proteins and glycolipids. Due to their location and large numbers per cell, these sugar molecules might be better targets for tumor imaging than proteins.

Real-time tumor imaging techniques are increasingly used in oncological surgery, but still need to be supplemented with novel targeted tracers, providing specific tumor tissue detection based on intra-tumoral processes or protein expression. To maximize tumor/non-tumor contrast, targets should be highly and homogenously expressed on tumor tissue only, preferably from the earliest developmental stage onward. Unfortunately, most evaluated tumor-associated proteins appear not to meet all of these criteria. Thus, the quest for ideal targets continues. Aberrant glycosylation of proteins and lipids is a fundamental hallmark of almost all cancer types and contributes to tumor progression. Additionally, overexpression of glycoproteins that carry aberrant glycans, such as mucins and proteoglycans, is observed. Selected tumor-associated glyco-antigens are abundantly expressed and could, thus, be ideal candidates for targeted tumor imaging. Nevertheless, glycan-based tumor imaging is still in its infancy. In this review, we highlight the potential of glycans, and heavily glycosylated proteoglycans and mucins as targets for multimodal tumor imaging by discussing the preclinical and clinical accomplishments within this field. Additionally, we describe the major advantages and limitations of targeting glycans compared to cancer-associated proteins. Lastly, by providing a brief overview of the most attractive tumor-associated glycans and glycosylated proteins in association with their respective tumor types, we set out the way for implementing glycan-based imaging in a clinical practice.

• aberrant glycosylation
• biomarkers
• cancer
• carbohydrates
• gangliosides
• molecular imaging
• mucins
• proteoglycans

• MR/M015564/1 Medical Research Council

• Glypican-3 (GPC3)
• Hepatocellular carcinoma (HCC)
• Wnt signaling

• Glypican
• HCC
• HCV
• miR-1291
• qRT-PCR

Hepatocellular carcinoma (HCC) is the third leading cause of cancer death, causing about 750000 deaths worldwide every year. Patients with advanced hepatocellular carcinoma will often only receive transcatheter arterial chemoembolization (TACE). Glypican-3 (GPC3) is one of the most promising serum markers for HCC. Abnormal expression of miRNAs may be involved in the occurrence and development of tumor.

To explore the value of miR-1271 and GPC3 in evaluating the prognosis of patients with HCC after TACE.

From January 2016 to December 2018, 162 patients with advanced HCC who received TACE in our hospital were selected into the cancer group, and 162 patients who underwent physical examination during the same period were selected into the health group. The patients in the HCC group were treated with TACE. The changes of serum GPC3 and circulating miR-1271 in the HCC before and after TACE were analyzed. The expression of serum GPC3 was detected by enzyme-linked immunosorbent assay, and the expression of circulating miR-1271 was detected by real-time quantitative polymerase chain reaction. The methodological results of sensitivity, specificity, and accuracy of miR-1271 and GPC3 alone and joint detection of HCC were also evaluated.

The level of serum GPC3 in patients with HCC was significantly higher than that in healthy controls. GPC3 levels were increased in both HCC patients and those treated with TACE compared with healthy controls. After TACE, the level of serum GPC3 was significantly lower than that before treatment (P < 0.05), and the level of circulating miR-1271 was significantly higher than that before treatment (P < 0.05). There were 112 cases (69.14%) with remission (complete remission + complete remission + stable disease) and 50 cases (30.86%) with relapse disease progression in HCC patients. After TACE, the miR-1271 level in patients with remission and relapse was lower than that in the healthy group, and the GPC3 level was higher than that in the healthy group, the differences were statistically significant (P < 0.05). The miR-1271 of relapsed patients was lower than that of remission patients, and the level of GPC3 was higher than that of remission patients, and the difference was statistically significant (P < 0.05). The sensitivity of combined detection of miR-1271 and GPC3 was significantly higher than that of single detection, and the difference was statistically significant (P < 0.05); while the specificity of the two combined detections was lower than that of the single detection; and the accuracy was slightly higher than that of single detection, but the difference was not statistically significant.

The level of miR-1271 in patients with HCC was significantly increased and the level of GPC3 was decreased after TACE. Monitoring the levels of serum GPC3 and circulating miR-1271 has important clinical reference value for evaluating the prognosis of patients with HCC. The levels of serum GPC3 and circulating miR-1271 may help to determine tumor recurrence, evaluate survival status, and guide the next step of treatment.

• miR-1271
• Glypican-3
• Hepatocellular carcinoma
• Transcatheter arterial chemoembolization
• Real-time quantitative polymerase chain reaction
• Tumor recurrence

• Anticancer drug resistance
• CAR-T
• Hepatocellular carcinoma
• Immune checkpoint inhibitors
• Predictive host and somatic genetic markers
• Tyrosine kinase inhibitors

• glypican 3
• hepatocellular carcinoma
• nomogram
• noninvasive
• radiomics

In this retrospective study, we investigated clinicopathological features and prognosis of hepatocellular carcinoma (HCC) patients applying an immunosubtyping method based on the serum α-fetoprotein (AFP) levels and glypican-3 (GPC3) immunohistochemical expression.

Two hundred and twenty-nine HCC patients, who had been subjected to hepatectomy and accepted serum AFP and GPC immunohistochemical expression tests, were divided into four groups: AFP⁺GPC3⁺, AFP⁺GPC3^–, AFP^–GPC3⁺, and AFP^–GPC3^– groups. During the study, HCC patients’ sex ratios, ages, incidence of cirrhosis, clinicopathological features—such as tumor lesion, tumor size, histological grade, vascular invasion, regional lymph node involvement, distant metastasis—and their follow-up time were observed and continuously recorded.

Regarding their clinicopathological features, the four groups only differed in the histological grade with statistical significance. Furthermore, the four subtypes showed statistically significant differences in sex ratios and incidence of cirrhosis. Among the four subtypes, the prognosis was just statistically different between the AFP⁺GPC3⁺ and AFP^–GPC3⁺ groups, and AFP^–GPC3⁺ was associated with a better prognosis.

A new HCC subtype could guide the personalized therapy of HCC patients to a certain extent. The four different subtypes resulting from the AFP- and GPC3-based subclassification of HCC, especially for AFP⁺GPC3⁺ and AFP⁻GPC3⁻ groups, were meaningful prognostic markers for HCC.

• Hepatocellular carcinoma (HCC)
• glypican-3 (GPC3)
• prognosis
• subtype
• α-fetoprotein (AFP)

• Clear cell carcinoma
• GPC3
• Glypican
• Immunotherapy
• Oncofetal
• Ovarian cancer

• Biomarkers, Tumor/analysis
• Canada
• Carcinoma/chemistry
• Carcinoma/immunology
• Carcinoma/pathology
• Carcinoma/therapy
• Chemotherapy, Adjuvant
• Female
• Glypicans/analysis
• Humans
• Immunohistochemistry
• Immunotherapy
• Middle Aged
• Ovarian Neoplasms/chemistry
• Ovarian Neoplasms/immunology
• Ovarian Neoplasms/pathology
• Ovarian Neoplasms/therapy
• Predictive Value of Tests
• Reproducibility of Results
• Retrospective Studies
• Tissue Array Analysis
• Treatment Outcome
• Up-Regulation

• Biomarker
• Diagnosis
• Hepatocellular carcinoma
• Prognosis
• Proteomics

• GP73
• HCC
• meta-analysis
• prognosis

Hepatocellular carcinoma (HCC) is one of the histological types of primary liver cancer with high recurrence and mortality in the world. The purpose of this study was to explore the diagnostic and therapeutic value for HCC patients.

In this study, we investigated the circulating miR‐130b‐5p (miR‐130b) and miR‐21‐5p (miR‐21) expression levels in patients with HCC and their association with clinical parameters.

The circulating miR‐130b and miR‐21 were all upregulated in patients with HCC. The upregulated microRNAs (miRNAs) were associated with clinicopathological parameters of tumor capsular infiltration and clinical TNM stage. Also, the poor prognosis of patients with upregulated miRNAs levels suggested that it may be an effective therapeutic target for HCC by suppression of the miRNAs levels. In addition, the combined detection of serum miR‐130b and miR‐21 performed better in the diagnosis of HCC with a sensitivity of 92.16% and an accuracy rate of 77.51%. In vivo, tumors treated with the nanoparticle (NP)/miR‐130b and miR‐21 inhibitor complexes had significantly lower growth than the other groups.

The circulating miR‐130b and miR‐21 can be used as potential tumor biomarkers to diagnose liver cancer, and the combined detection of serum miR‐130b and miR‐21 is superior to the diagnosis of HCC. NP/miR‐130b and miR‐21 inhibitor complexes show good therapeutic effects in vivo and are expected to become therapeutic targets worthy of further study.

• biomarker
• hepatocellular carcinoma
• miR-130b
• miR-21
• nanoparticle
• therapeutic target

• glypican 3
• hepatocellular carcinoma
• hepatoma
• normal alpha-fetoprotein

• CMRPG3G1301 Chang Gung Memorial Hospital, Linkou
• CMRPG3I0301 Chang Gung Memorial Hospital, Linkou
• MOST 107-2314-B-182A-119- / NMRPG3H0291 Ministry of Science and Technology, Taiwan, R.O.C.

• AEG-1
• Diagnosis
• GPC-3
• Hepatocellular carcinoma

• CAR-T
• HCC
• Immunotherapy
• immune checkpoint inhibitors
• vaccination

Early diagnosis of hepatocellular carcinoma (HCC) greatly improves the survival and prognosisfor patients. In this study weevaluate the diagnostic promise of combining serum alpha-fetoprotein (AFP) expression with two potential biomarkers, serum glypican-3 (GPC3) and expression of the micro-RNA miR-122 for hepatitis C virus (HCV) related early-stage HCC. For this study serum samples from 47 patients with early-stage HCC, 54 chronic HCV (CH) carriers, 35 patients with liver cirrhosis (LC) and 54 health controls (HC) were collected. In addition to routine laboratory investigations, serum AFP, GPC3 and miR-122 were measured in all patients and healthy controls. Receiver operating characteristic (ROC) curves were used to present sensitivity and specificity for the biomarkers. The three markers were all significantly elevated in the serum samples from HCC patients. ROC curves showed the three markers had similar diagnostic capacities for distinguishing early-stage HCC from HCV-positive controls (LC + CH). In order to distinguish early-stage HCC from high-risk LC patients, the expression of miR-122 was superior to GPC3. Combination of the three markers as a panel showed a better diagnostic performance than any of the single markers (P <0.05). Overall, this study revealed that serum expression of GPC3 and miR-122 may be useful biomarkers to combine with serum AFP expression for the diagnosis of HCV related early-stage HCC.

• Alpha-fetoprotein
• Glypican-3
• Hepatitis C virus
• Hepatocellular carcinoma
• Liver fibrosis
• miR-122

• GP73
• hepatitis
• liver cancer
• liver cirrhosis

• Animals
• Carcinoma, Hepatocellular/diagnosis
• Carcinoma, Hepatocellular/pathology
• Hepatitis/diagnosis
• Hepatitis/pathology
• Hepatocytes/pathology
• Humans
• Liver/pathology
• Liver Cirrhosis/diagnosis
• Liver Cirrhosis/pathology
• Liver Diseases/diagnosis
• Liver Diseases/pathology
• Liver Neoplasms/diagnosis
• Liver Neoplasms/pathology
• Membrane Proteins/analysis
• Prognosis

• BJ16003 Health Care for Cadres Research Fund of Jiangsu Province
• ZDRCA2016065 Jiangsu Province Medical Talent
• 61527806 National Natural Scientific Foundation of China
• 61741114 National Natural Scientific Foundation of China
• 81472831 National Natural Scientific Foundation of China
• 81700790 National Natural Scientific Foundation of China
• 201705 Opening Project of State Key Laboratory of Bioelectronics
• BE2016625 Key Research and Development Project of Jiangsu Province
• 201715020 Science and Technology Development Program of Nanjing
• ZKX16045 Medical Key Science and Technology Development Projects of Nanjing
• SKLOD2018OF02 Open Funding of State Key Laboratory of Oral Diseases

• Alpha fetoprotein
• Biomarker
• Liver cirrhosis
• Sensitivity
• Specificity

• Biomarkers, Tumor/blood
• Carcinoma, Hepatocellular/blood
• Carcinoma, Hepatocellular/diagnosis
• Glypicans/blood
• Humans
• Liver Neoplasms/blood
• Liver Neoplasms/diagnosis
• Reproducibility of Results

• Glypican-3
• diagnosis accuracy
• hepatocellular carcinoma
• meta-analysis

• ovarian germ cell
• postmenopausal
• prognosis
• yolk sac tumor

• Aged
• Antineoplastic Combined Chemotherapy Protocols/administration & dosage
• Endodermal Sinus Tumor/pathology
• Endodermal Sinus Tumor/therapy
• Female
• Humans
• Middle Aged
• Ovarian Neoplasms/pathology
• Ovarian Neoplasms/therapy
• Ovary/surgery
• Postmenopause
• Prognosis

The aim of the present study was to investigate the biological role of glypican 3 (GPC3), and to identify its mechanism and clinical significance in the carcinogenesis of liver cancer. A total of 114 patients with liver cancer were involved. Their clinical data, hematoxylin and eosin-stained and Antigen Ki-67 protein (Ki-67) and GPC3 immunohistochemically-stained liver cancer tissue sections were analyzed to evaluate the correlation between the liver cancer proliferation, differentiation and GPC3 expression. Fluorescence microscopy, western blotting, MTT and reverse transcription quantitative polymerase chain reaction (RT-qPCR) assays were performed in HepG2 and HLE cell lines to investigate the potential mechanisms of action. Among the 114 patients with liver cancer enrolled in the present study, 12 exhibited well-differentiated liver cancer, of which 6 (50%) were positive for GPC3. A total of 30 cases exhibited poorly differentiated liver cancer; 26 (87%) of these expressed GPC3 and 11 cases (37%) demonstrated strong positive expression levels. The other 72 liver cancer cases were moderately differentiated; 75% (54/72) of these expressed GPC3 and 12.5% (9/72) exhibited strong positive expression levels. There was a significant association between the levels of GPC3 expression and liver cancer differentiation (χ²=16.306, P=0.008). Ki-67 staining as the criteria of the liver cancer cell proliferation index also indicated a cross correlation between liver cancer proliferation and GPC3 levels. Among the 39 liver cancer samples with a cell proliferation index <5%, only 2.6% (1/39) exhibited strong positive GPC3 staining, but of the 16 cases with a high cell proliferation index >50%, 6 exhibited strong GPC3 staining (37.5%). The difference of cell proliferation indexes between cancer cells were well, moderate and poorly differentiated, and was markedly significant (χ²=26.334, P=0.002), and suggested that liver cancer cell proliferation was positively correlated with GPC3 expression (r=0.316, P=0.001). Consistently, in vitro analysis indicated that GPC3 promoted HepG2 and HLE cell growth, which was more apparent in HepG2 cells. The RT-qPCR results indicated that GPC3 promoted proliferation through the Hedgehog (Hh) pathway in HepG2 cells, but not in HLE cells. In the present study, it was demonstrated that patients with liver cancer with higher GPC3 levels exhibited poorer differentiation and higher proliferation levels. In vitro GPC3 may promote liver cancer cell lines proliferation through the Hh pathway.

• antigen Ki-67
• differentiation
• glypican 3
• liver cancer
• proliferation

• Glypican-3
• AFP
• HCC
• diagnostic sensitivity

• Adult
• Biomarkers, Tumor/blood
• Carcinoma, Hepatocellular/blood
• Carcinoma, Hepatocellular/diagnosis
• Case-Control Studies
• Female
• Follow-Up Studies
• Glypicans/blood
• Humans
• Liver Neoplasms/blood
• Liver Neoplasms/diagnosis
• Male
• Middle Aged
• Prognosis
• ROC Curve
• alpha-Fetoproteins/analysis

• Fluorescent imaging
• Glypican-3
• Hepatocellular carcinoma
• PET
• Targeting peptide probe

• Animals
• Biomarkers, Tumor
• Carcinoma, Hepatocellular/diagnostic imaging
• Carcinoma, Hepatocellular/metabolism
• Carcinoma, Hepatocellular/pathology
• Cell Line
• Disease Models, Animal
• Female
• Fluoresceins/chemistry
• Fluorine Radioisotopes/chemistry
• Glypicans/metabolism
• Hep G2 Cells
• Humans
• Liver/cytology
• Liver/metabolism
• Liver/pathology
• Liver Neoplasms/diagnostic imaging
• Liver Neoplasms/metabolism
• Liver Neoplasms/pathology
• Male
• Mice
• Muscles/metabolism
• Oligopeptides/chemical synthesis
• Oligopeptides/chemistry
• Oligopeptides/metabolism
• Oligopeptides/pharmacokinetics
• Organ Specificity
• Positron-Emission Tomography
• Protein Stability
• Tissue Distribution

• 81071175 National Natural Science Foundation Project of China
• 81371591 National Natural Science Foundation Project of China
• 2014A030313311 Natural Science Foundation Project of Guangdong Province

Glypican-3 (GPC3) is a promising new marker for hepatocellular carcinoma, but the reported values for serum GPC3 differ markedly between currently available kits. Here we isolated Affimer non-antibody binding proteins against GPC3 by phage display and developed a new sandwich chemiluminescence immunoassay (CLIA) combining an Affimer with a monoclonal antibody (Affimer-MAb CLIA). The proposed CLIA assay demonstrated a wide linear range  0.03–600 ng/mL) with a good linear correlation coefficient (0.9999), a high detection limitation (0.03 ng/mL) and specificity (0–0.002%) for detection of GPC3. The accuracy, hook effect and stability were demonstrated to be satisfactory. The mean level of GPC3 in serum was higher (>8.5 fold, P < 0.001) in hepatocellular carcinoma patients compared to healthy and other liver disease individuals. A poor correlation (correlation coefficients ranged from −0.286 to 0.478) was observed through pairwise comparison within different kits. However, only this newly developed CLIA test showed high specificity and correlated with the “gold standard” GPC3-immunohistochemistry. This study indicates that Affimer-MAb CLIA can be used to generate a sensitive immunodiagnostic kit, which offers the potential for a highly specific clinically-relevant detection system.

• 原发性肝细胞肝癌
• 肿瘤标志物
• 磷酯酰肌醇蛋白聚糖-3
• 甲胎蛋白
• primary hepatocellular carcinoma
• tumor markers
• glypican-3
• alpha fetoprotein

Esophageal cancer-related gene 4 (ECRG4) is a candidate tumor suppressor gene, which is involved in cell apoptosis, migration, infection and inflammation responsiveness; however, its expression level and clinical significance in hepatocellular carcinoma (HCC) remains unclear. In the present study, the authors aim to evaluate the clinical significance and potential role of ECRG4 in HCC. Level of ECRG4 protein expression in HCC and peripheral tissues was investigated in tissue specimens obtained from 56 consecutive HCC patients by immunohistochemistry. Cell proliferation, cell migration and invasion regulations were examined by MTT curves, flow cytometry, Transwell assays and western blotting. ECRG4 expression was weak positive in normal liver cells but was downregulated in HCC cells in vivo or in vitro. A decreased expression of ECRG4 was associated with the age of the patients, metastasis and Ki-67 proliferation index. However, decreased ECRG4 expression was not associated with differentiation, tumor size, the presence of portal vein tumor thrombosis, satellite lesions, tumor relapse or mortality. Further investigations revealed that ectopic expression of ECRG4 inhibited cell proliferation, migration and invasion and promoted cell apoptosis in SMMC-7721 cells, which was mediated by the regulation of BAX and B cell lymphoma-2, in addition to the upregulation of epithelial-mesenchymal transition markers. In conclusion, the results of the present study indicated that ECRG4 was downregulated in HCC and served important roles in promoting cell proliferation and migration.

• esophageal cancer-related gene 4
• hepatocellular carcinoma
• immunohistochemistry
• western blotting

Increasing evidence indicates that in hepatocellular carcinomas (HCCs) abnormal gene expression, for example of glypican-3 (GPC-3) and insulin-like growth factor-II (IGF-II), are associated with the occurrence and progression of HCC. The objective of this study was to evaluate the differential expression of GPC-3 and IGF-II mRNAs in HCC tissues with a background of chronic hepatitis C virus (HCV) genotype 4 cirrhosis, in relation to Ki-67 and alpha-feto protein (AFP) tissue markers.

One hundred and five patients with HCCs who had undergone hepatectomy, were included, after obtaining informed consent. Total RNA was extracted from malignant and corresponding peri-malignant liver tissues, and GPC-3 and IGF-II mRNAs in addition to beta-actin mRNA as an internal control, were evaluated in all samples by reverse transcriptase-polymerase chain reactions (RT-PCR). Routine histopathological diagnosis as well as immunohistochemical (IHC) staining using monoclonal antibodies for Ki-67 and AFP were also performed.

Expression of GPC-3 mRNA was positive in all HCC malignant tissue, with overexpression in 86/105 (81.9%); in respect to the grade of the tumor (1-3 grades), while in peri-malignant tissue it was over expressed only in 20/105 (19%). The IGF-II mRNA was over expressed in only 10/105 (9.5%) malignant and peri-malignant samples. AFP was expressed in 33.3% of malignant samples but absent in peri-malignant tissues. Ki-67 expression was significantly increased in malignant compared to peri-malignant tissue.

GPC-3 and IGF II mRNAs may be good molecular markers for HCC, especially with a background of cirrhosis due to chronic HCV infection. Significant correlations were noted with the pattern of AFP and Ki-67 expression.

• Glypican-3
• Insulin–Like Growth Factor-II
• hepatocellular carcinoma
• HCV
• alpha-fetoprotein

• ELISA
• glypican-3
• hepatocellular carcinoma
• serum
• α-fetoprotein

• Biomarkers, Tumor/blood
• Carcinoma, Hepatocellular/blood
• Carcinoma, Hepatocellular/diagnosis
• Carcinoma, Hepatocellular/metabolism
• Enzyme-Linked Immunosorbent Assay/methods
• Female
• Glypicans/blood
• Humans
• Liver Cirrhosis/blood
• Liver Cirrhosis/diagnosis
• Liver Neoplasms/blood
• Liver Neoplasms/diagnosis
• Liver Neoplasms/metabolism
• Male
• Middle Aged
• ROC Curve
• Sensitivity and Specificity
• alpha-Fetoproteins/metabolism

Glypican-3 (GPC3), a member of heparan sulfate proteoglycans, attaches to the cell membrane and is frequently observed to be elevated in hepatocellular carcinoma (HCC). However, GPC3 is not detected in normal liver tissues and benign liver lesions. Consequently, GPC3 is currently being used as a diagnostic biomarker and HCC-specific positron emission computed tomography probe to identify HCCs in normal liver tissues and benign liver lesions. The overexpression of GPC-3 in serum or liver tissue also predicts poor prognosis for HCC patients. In addition, GPC3 promotes HCC growth and metastasis by activating the canonical Wnt and other signaling pathways. Targeting of GPC3, including GC33, HN3 and YP7, might offer new immunotherapeutic tools for HCC treatment.

• diagnostics
• glypican-3
• hepatocellular carcinoma
• immunotherapy
• prognosis

• Biomarkers
• Diagnosis
• Glypican-3
• Hepatocellular carcinoma
• Serum
• α-fetoprotein

• Adult
• Aged
• Bilirubin/blood
• Biomarkers, Tumor/blood
• Carcinoma, Hepatocellular/blood
• Carcinoma, Hepatocellular/diagnosis
• Carcinoma, Hepatocellular/pathology
• Glypicans/blood
• Humans
• Liver Neoplasms/blood
• Liver Neoplasms/diagnosis
• Liver Neoplasms/pathology
• Middle Aged
• alpha-Fetoproteins/analysis