Golgi Protein 73 Research Articles

Magnetic Nanoparticle-Based Automatic Chemiluminescent Enzyme Immunoassay for Golgi Protein 73 and the Clinical Assessment.

Golgi protein 73 (GP73) is an independent diagnostic indicator of cirrhosis. However, it lacks automatic detection techniques to meet the large-scale clinical requirement in physical examination. In this paper, an automatic approach was established based on the ACL2800 automatic chemiluminescent analyzer, using magnetic nanoparticles (MNPs) and chemiluminescence. This method depended on sandwich strategy among biotin-labeled capture monoclonal antibody, target GP73 and acridinium ester (AE)-labeled reporter monoclonal antibody, conjugation of streptavidin-labeled MNPs to biotin-labeled capture monoclonal antibody, and chemiluminescent detection of AE-linked targets. Optimal conditions were investigated and clinical assessment was processed. Detection of GP73 demonstrated a high sensitivity of 1.19 ng/mL with a wide range from 1.34 ng/mL to 684.38 ng/mL. The quantitative detection was achieved with the repeatability of 2.69%, the coefficient of variation of 3.55% and the percent recovery of 93.46%-107.82%. Therefore, an automatic quantitative detection method was successfully developed, which was a potential screening method in physical examination.

A meta-analysis of the prognostic significance of Golgi protein 73 in hepatocellular carcinoma in Chinese patients.

IntroductionIn recent years, an increasing number of studies have revealed the possible prognostic significance of Golgi protein 73 (GP73) in hepatocellular carcinoma (HCC), but the results are still controversial. Therefore, we performed a meta-analysis to explore the possible correlation between GP73 and prognostic value in HCC.Material and methodsRelevant publications were searched for in PubMed, EMBASE, Cochrane Library and the Chinese Biomedical Literature Database up to March 2018. Odds ratios (ORs) or hazard ratios (HRs) and 95% confidence intervals (CI) of eligible studies were assessed by either fixed-effect or random effects models. Publication bias analysis was also performed to assess the reliability of the meta-analysis results.ResultsIn total, 9 studies including 1292 patients with HCC were included and analysed systematically in the study. The results indicated that GP73 overexpression was significantly associated with later tumour stage, higher tumour grade and poor overall survival (OS). Combined analysis of three studies showed no statistical correlation between high GP73 expression and disease-free survival (DFS). Subgroup analyses were also performed to illustrate the relationship between high GP73 expression and OS.ConclusionsThe meta-analysis suggested that overexpression of GP73 may be associated with poor prognosis in HCC and may also have a predictive role for HCC invasion and metastasis.

Serum GP73 combined AST and GGT reflects moderate to severe liver inflammation in chronic hepatitis B

BackgroundNon-invasive method to identify chronic hepatitis B (CHB) patients with at least moderate inflammatory lesion but no increased ALT is an unmet need.We evaluated Golgi protein 73 (GP73) based hepatic inflammation model (HIM) as a serum surrogate for liver necroinflammatory activity, especially in those with ALT less than traditional upper concentration. MethodsThe diagnostic performances of HIM were evaluated in 2 independent cohorts of liver biopsy proved CHB patients by receiver operating characteristic (ROC) curve analysis. ResultsHIM, a suggested index combined GP73, gamma-glutamyltransferase and AST, could significantly improve the diagnostic accuracy for liver necroinflammation (Area under ROC, AUROC: 0.890). More importantly, HIM still exhibit excellent diagnostic value (AUROC: 0.873) to identify patients with at least moderate liver necroinflammatory activity but with ALT <40 U/l. Serum GP73 was the major source of improvement for diagnostic model's accuracy. ConclusionHIM is probably a promising non-invasive index to identify CHB patients with moderate to severe liver necroinflammation, especially in those with ALT <40 U/l.

Ratiometric Immunosensor for GP73 Detection Based on the Ratios of Electrochemiluminescence and Electrochemical Signal Using DNA Tetrahedral Nanostructure as the Carrier of Stable Reference Signal.

DNA tetrahedron nanostructure (DTNs) has the merits of simple synthesis, high yield, structural stability, and mechanical rigidity, and its three-dimensional structure provides a satisfactory biosensing interface to the improvement of the binding efficiency of antigenic proteins and antibodies. Electrochemiluminescence (ECL) reagent, tris(4,4'-dicarboxylicacid-2,2'-bipyridyl)ruthenium(II) dichloride (Ru(dcbpy)3Cl2), was modified on the electrode through the formation of classical sandwich complex of antibody-antigen-antibody. ECL response of the system increased with the increment of the target (golgi protein 73 (GP73) in this study) with high selectivity. Besides, the composed double-stranded DNA (dsDNA) in each side of DTNs could act as an excellent carrier of methylene blue (MB), thus producing a stable electrochemical internal reference signal on the electrode surface to correct the potential interferences. Therefore, a highly selective and reproductive ratiometric immunosensor was developed on the basis of the ratio of ECL of Ru(dcbpy)3Cl2 and electrochemistry of MB. The ratio value of the ECL/electrochemistry had a linear relationship with GP73 concentration in the range of 15 pg/mL-0.7 ng/mL, and the limit of detection was 15 pg/mL. The proposed ratiometric ECL immunoassay has been applied to detect GP73 in real serum samples with satisfactory results.

Clinicopathological significance of miR-27b targeting Golgi protein 73 in patients with hepatocellular carcinoma.

Using five bioinformatics analysis software, we identified Golgi protein 73 (GP73) as a putative target of microRNA-27b (miR-27b), which is closely related to various biological processes or diseases such as bone metabolism disease, adipose cell and muscle cell development, pulmonary hypertension, cervical cancer, and breast cancer. However, the clinical significance of miR-27b in hepatocellular carcinoma (HCC) is still unclear. The differential expression of miR-27b in HCC and adjacent normal liver tissues was measured by quantitative reverse transcription PCR. Our results showed that the expression of miR-27b in tumor tissues is lower than that in adjacent nontumor tissues. The expression of miR-27b was significantly lower in HCC tissues with high expression of GP73, when compared with adjacent nontumor tissues. Moreover, down-regulated expression of miR-27b was closely correlated with serum GP73, tumor-node-metastasis stage, tumor size, and portal vein thrombosis. GP73 mRNA might be a target of miR-27b. The 5-year overall survival rate of the low miR-27b expression group was significantly lower than that of the high miR-27b expression group. Moreover, multivariate analysis of prognostic factors, with a Cox proportional hazards model, showed that low miR-27b expression was a significant and independent predictor of poor survival in HCC. Hence, the abnormal expression of miR-27b might be related to the occurrence and development of tumors. Similarly, a study in the Cancer Genome Atlas database demonstrated that the expression of miR-27b in 50 normal individuals was 1.6 times higher than that of 372 patients with liver cancer. The overall survival rate of the low GP73 expression group (275 liver cancer patients) was significantly longer than that of the high GP73 expression group (90 normal individuals). MiR-27b suppresses the expression of GP73 and is therefore a potential prognostic biomarker and therapy target in HCC.

Serum Golgi protein 73 is a marker comparable to APRI for diagnosing significant fibrosis in children with liver disease

Serum Golgi protein 73 (GP73) is a promising marker for significant fibrosis in adults. However, current diagnostic value of serum GP73 for liver fibrosis in children is unknown. To investigate the relationship between levels of serum GP73 and liver fibrosis in children, we measured serum GP73 in 86 healthy controls and 183 patients with liver diseases using commercially available double-antibody sandwich enzyme-linked immunosorbent assay (ELISA) kit. The value of serum GP73 in fibrosis stage assessment was compared with aspartate transaminase to platelet ratio index (APRI). We found that serum GP73 was decreasing with age in healthy controls, while it was increasing with the extent of inflammation and fibrosis in patients with liver diseases. Though area under the receiver operating curve (AUROC) of serum GP73 for diagnosing significant fibrosis was nearly equal to APRI (0.62 vs 0.64) in patients aged 3 years or older, AUROC for serum GP73 was superior to APRI (0.76 vs 0.67) in patients aged below 3 years, indicating that serum GP73 is comparable to APRI for diagnosing significant fibrosis in children.

Quantitative screening of serum protein biomarkers by reverse phase protein arrays.

Screening biomarkers in serum samples for different diseases has always been of great interest because it presents an early, reliable, and, most importantly, noninvasive means of diagnosis and prognosis. Reverse phase protein arrays (RPPAs) are a high-throughput platform that can measure single or limited sets of proteins from thousands of patients' samples in parallel. They have been widely used for detection of signaling molecules involved in diseases, especially cancers, and related regulation pathways in cell lysates. However, this approach has been difficult to adapt to serum samples. Previously, we developed a sensitive method called the enhanced protein array to quantitatively measure serum protein levels from large numbers of patient samples. Here, we further refine the technology on several fronts: 1. simplifying the experimental procedure; 2. optimizing multiple parameters to make the assay more robust, including the support matrix, signal reporting method, background control, and antibody validation; and 3. establishing a method for more accurate quantification. Using this technology, we quantitatively measured the expression levels of 10 proteins: alpha-fetoprotein (AFP), beta 2 microglobulin (B2M), Carcinoma Antigen 15-3(CA15-3), Carcinoembryonic antigen (CEA), golgi protein 73 (GP73), Growth differentiation factor 15 (GDF15), Human Epididymis Protein 4 (HE4), Insulin Like Growth Factor Binding Protein 2 (IGFBP2), osteopontin (OPN) and Beta-type platelet-derived growth factor receptor (PDGFRB) from serum samples of 132 hepatocellular carcinoma (HCC) patients and 78 healthy volunteers. We found that 6 protein expression levels are significantly increased in HCC patients. Statistical and bioinformatical analysis has revealed decent accuracy rates of individual proteins, ranging from 0.617 (B2M) to 0.908 (AFP) as diagnostic biomarkers to distinguish HCC from healthy controls. The combination of these 6 proteins as a specific HCC signature yielded a higher accuracy of 0.923 using linear discriminant analysis (LDA), logistic regression (LR), random forest (RF) and support vector machine (SVM) predictive model analyses. Our work reveals promise for using reverse phase protein arrays for biomarker discovery and validation in serum samples.

Overexpression of GP73 promotes cell invasion, migration and metastasis by inducing epithelial-mesenchymal transition in pancreatic cancer

Pancreatic cancer is one of the most difficult clinical cases to diagnose with a very low 5-year survival rate of 5%, regardless of the advances made in both the medical and surgical treatment of the disease. One of the contributing factors for the high mortality rate seen of pancreatic cancer patients is the lack of effective chemotherapies, which is believed to be due to drug-resistance. Based on recent evidence, epithelial-mesenchymal transition (ETM) of pancreatic cancer cells has been found to be associated with the development of drug resistance and an increase in cell invasion. Therefore, we conducted the present study in order to investigate the regulatory effects of Golgi protein-73 (GP73) on PC. GP73 and EMT-related gene expressions in PC, along with the adjacent and chronic pancreatitis tissues were determined by means of RT-qPCR and Western blot analysis. Cultured PC cells were treated with pAdTrack-CMV, si-NC, GP73 overexpression, Si-GP73, Snail-siRNA and GP73 + Snail-siRNA. Cell invasion, migration and metastasis were measured in vitro and in vivo. The results revealed that the PC tissues and chronic pancreatitis tissues exhibited diminished E-cadherin expression and amplified GP73, N-cadherin, Vimentin and Snail expression. In response to GP73 gene silencing, PC cells presented with increased E-cadherin expression and decreased N-cadherin, Vimentin, Snail expression in addition to the inhibition of the number of invasive cells, tumor volume and number of liver lesions. These findings highly indicated that the overexpression of GP73 promotes cell invasion, migration and metastasis by inducing EMT in PC.

Highly sensitive electrochemical immunosensor for golgi protein 73 based on proximity ligation assay and enzyme-powered recycling amplification

Golgi protein 73 (GP73) is a potential hepatocellular carcinoma serum marker with better sensitivity and specificity. In this study, a highly sensitive electrochemical immunosensor which combines the highly selective proximity ligation assay (PLA) and highly efficient enzyme-powered recycling amplification has been developed for GP73 determination. PLA is triggered by affinity binding of two labelled antibody-DNA (P1-RAb and P2-MAb) to target protein, resulting in increased specificity. The formed immunocomplex hybrids with DNA2 to realize the release of methylene blue labelled mononucleotides fragment with the help of exonuclease III, which acts as the power of recycling amplification. The fragment can diffuse easily to the nafion modified indium tin oxide electrode surface and a strong electrochemical signal can be detected. Under the optimized conditions, the enhanced electrochemical intensity has a linear relationship with the concentration of GP73 in the range of 0.3 pg mL−1 to 6.0 ng mL−1 with the detection limit of 0.10 pg mL−1. The developed immunosensor has been applied to detect the GP73 in the clinical serum samples with satisfactory results.

Hepatocellular Carcinoma: Causes, Mechanism of Progression and Biomarkers.

Hepatocellular Carcinoma (HCC) is one of the most common malignant tumours in the world. It is a heterogeneous group of a tumour that vary in risk factor and genetic and epigenetic alteration event. Mortality due to HCC in last fifteen years has increased. Multiple factors including viruses, chemicals, and inborn and acquired metabolic diseases are responsible for its development. HCC is closely associated with hepatitis B virus, and at least in some regions of the world with hepatitis C virus. Liver injury caused by viral factor affects many cellular processes such as cell signalling, apoptosis, transcription, DNA repair which in turn induce important effects on cell survival, growth, transformation and maintenance. Molecular mechanisms of hepatocellular carcinogenesis may vary depending on different factors and this is probably why a large set of mechanisms have been associated with these tumours. Various biomarkers including α-fetoprotein, des-γ-carboxyprothrombin, glypican-3, golgi protein-73, squamous cell carcinoma antigen, circulating miRNAs and altered DNA methylation pattern have shown diagnostic significance. This review article covers up key molecular pathway alterations, biomarkers for diagnosis of HCC, anti-HCC drugs and relevance of key molecule/pathway/receptor as a drug target.

Upregulated GP73 expression and downregulated NLRP3 expression in liver cancer tissues correlate with patient’s survival

Background: To investigate the correlation between Golgi protein 73 (GP73) and NLRP3 expression and the clinicopathologic features and prognosis in patients with hepatocellular carcinoma (HCC). Methods: A total of 54 HCC tumor tissues and matched paracarcinomatous liver (PCL) tissues from patients who received liver resection in our hospital were collected. The expression of GP73 and NLRP3 were tested by using Western blotting method. Eleven healthy liver (HL) tissues from patients with hepatic hemangioma were tested at the same time. Correlations between GP73/NLRP3 protein expression levels and clinicopathologic features were evaluated by Chi-square test. Survival analysis was conducted by Kaplan-Meier method, and overall survival (OS) and disease-free survival (DFS) were calculated, meanwhile the log-rank test was used to compare the survival differences between different groups. Results: The median GP73 protein level in HL, PCL and HCC tissues were 1.6 (1.4–1.9) RU, 2.7 (1.6–3.4) RU and 4.5 (2.8–5.5) RU, respectively. The median NLRP3 protein level in HL, PCL and HCC tissues were 1.1 (0.9–1.3) RU, 1.9 (1.4–2.6) RU and 1.2 (0.4–1.3) RU, respectively. They were both with significant difference (P Conclusions: GP73 and NLRP3 may play the role of different level in tumor development in patients with HCC. NLRP3 could have more effect on DFS.

Development of an alpha-fetoprotein and Golgi protein 73 multiplex detection assay using xMAP technology

Development of a new method to simultaneously detect Alpha-fetoprotein (AFP) and Golgi protein 73 (GP73) from peripheral blood. Anti human AFP and GP73 monoclonal antibodies was used to develop a sandwich immunity reaction using xMAP technology for the simultaneous detection of plasma AFP and GP73. The assay evaluated the sensitivity, cross reactivity, range of detection, precision, recovery and linearity dilution effect. The assay utilized plasma samples and compared its performance with commercially available Enzyme Linked Immunosorbent Assay (ELISA) kits. The assay was successful in detecting AFP and GP73 simultaneously. Validation experiments demonstrated the limit of detection was AFP 0.006 μg/l and GP73 0.482 μg/l. The functional sensitivity was AFP 0.010 μg/l and GP73 0.640 μg/l. The range of detection was AFP 0.01-50 μg/l and GP73 0.64-100 μg/l. No cross reactivity was observed. The intra- and inter-assay variation for AFP was 0.19-3.46% and 3.1-5.8% and for GP73 was 1.5-3.2% and 1.1-7.6% respectively. The recovery for AFP was 96-106% and GP73 was 89-110%. 80 clinical plasma samples from healthy controls, and patients with liver cirrhosis and Hepatocellular Carcinoma (HCC) were evaluated. For healthy controls (n = 25), the AFP was 2.40 (1.55, 3.30) μg/l and GP73 was 42.60 (39.10, 57.40) μg/l. For patients with liver cirrhosis (n = 19), the AFP was 2.60 (1.70, 4.20) μg/l and GP73 was 136.10 (92.10, 261.70) μg/l, and for HCC patients (n = 36), the AFP was 13.65 (3.35, 158.88) μg/l and GP73 was 186.25 (96.73, 262.03) μg/l. The new assay demonstrated a good correlation with commercially available ELISA kits (correlation coefficients (r) were 0.997 (AFP, p < 0.001) and 0.959 (GP73, p < 0.001). The method demonstrated a sensitive, effective and accurate method for the simultaneous detection of AFP and GP73, and could be used clinically for routine detection and monitoring of patients with chronic hepatitis B.

Upregulated GP73 expression and downregulated NLRP3 expression in liver cancer tissues correlate with patient’s survival

Background: To investigate the correlation between Golgi protein 73 (GP73) and NLRP3 expression and the clinicopathologic features and prognosis in patients with hepatocellular carcinoma (HCC).

Hepatitis B virus upregulates GP73 expression by activating the HIF-2α signaling pathway.

Golgi Protein 73 (GP73) is a newly identified diagnostic and prognostic marker for liver cancer. GP73 is highly expressed in liver cancer tissues, however, the mechanism of its overexpression in tumors remains unknown. In the present study, the effect of hepatitis B virus (HBV) on GP73 expression was investigated in HepG2 cells, which are negative for HBV, and in HepG2.2.12 cells, which are integrated with HBV, using reverse transcription-quantitative polymerase chain reaction and western blot analysis. In addition, the cells were transfected with plasmid constructs overexpressing hepatitis B virus protein X (HBx), hypoxia-inducible factor (HIF)-1α, or HIF-2α in order to examine their roles in GP73 expression. The results demonstrated that HBV upregulated the expression of GP73 and HIF-2α in liver cancer cells. HIF-2α induced the expression of GP73 in HepG2 cells and was positively correlated with GP73 expression in liver cancer tissues. By contrast, HBx and HIF-1α did not induce GP73 expression in liver cancer cells. In summary, HBV may upregulate the expression of GP73 by activating the HIF-2α signaling pathway. The present results may illuminate the mechanism by which GP73 is overexpressed in liver cancer tissues.

Expression and correlation of CD44 and GP73 in cerebroma tissues.

Cerebroma, a nervous system tumor located in the cranial cavity, seriously affects health and may even become life-threatening. The aim of the study was to investigate and discuss the expression levels of cluster of differentiation 44 (CD44) and Golgi protein 73 (GP73) in different types of cerebroma tissues and to study the correlations of CD44 and GP73. Reverse transcription-polymerase chain reaction (RT-PCR) was used to detect the mRNA expression levels of CD44 and GP73 in four kinds of cerebroma. The immunohistochemical streptavidin-biotin complex (SABC) method was applied to measure the expression levels of CD44 and GP73 in different types of cerebroma. Subsequently, immunofluorescence and western blot analysis were performed to detect the expression levels of CD44 and GP73 in four kinds of cerebroma tissues. Statistical Product and Service Solutions (SPSS) 17.0 software was used to analyze the differences in CD44 and GP73 expression levels of the four kinds of cerebroma tissues and normal brain tissues. Transcription of CD44 and GP73 mRNAs was detected in the four kinds of cerebroma tissues, and CD44 and GP73 proteins were expressed. The immunohistochemical results revealed that the expression levels of CD44 and GP73 in the four kinds of cerebroma were significantly increased compared with those in normal tissues. The immunofluorescence results indicated that both CD44 and GP73 were expressed in four kinds of cerebroma, and the expression of CD44 was higher than that of GP73. The results of analysis of variance showed that the differences in CD44 and GP73 expression levels in the four kinds of cerebroma tissues and normal brain tissues were statistically significant (P<0.01). The results show that the expression levels of CD44 and GP73 are obviously upregulated in four kinds of cerebroma tissues, suggesting that CD44 and GP73 have great value for cerebroma research and can provide a new direction for clinical study as well as the diagnosis and treatment of cerebroma.

GP73 promotes epithelial-mesenchymal transition and invasion partly by activating TGF-β1/Smad2 signaling in hepatocellular carcinoma.

The transforming growth factor-β1 (TGF-β1) signaling pathways contribute to cell metastasis and epithelial-mesenchymal transition (EMT). Golgi protein 73 (GP73), a type II transmembrane protein in the Golgi apparatus, was initially regarded as a potential biomarker for the diagnosis of hepatocellular carcinoma (HCC). Recently, it was reported that GP73 acts as a key oncogene by promoting HCC growth and metastasis. However, the role of GP73 in metastasis, especially when involving signaling pathways, is uncertain. Here, we report that GP73, which is upregulated in HCC tissues and cell lines, is associated with tumor size, tumor node metastasis stage, distant metastasis and vascular invasion. The ectopic overexpression of GP73 increased HCC cell invasion, EMT and metastasis both in vitro and in vivo. Conversely, GP73 knockdown inhibited invasion and EMT. Moreover, GP73 enhanced p-Smad2 and p-Smad3 levels by mediating TGF-β1, thus leading to the promotion of EMT and invasion in HCC cells. In contrast, we used SB431542 (SB) to repress p-Smad2 and p-Smad3 expression, which resulted in a reversion of EMT. Furthermore, when the TGF-β1/Smad pathway was blocked, upregulation of GP73 still caused an enhanced EMT and invasion, and downregulation of GP73 resulted in a decreased in EMT and invasion. In clinical HCC samples, GP73 positively correlated with TGF-β1/Smad2, which was upregulated in HCC. Taken together, our findings highlight the important role of GP73 in regulating EMT and metastasis in HCC partly by targeting TGF-β1/Smad2 signaling, suggesting that GP73 may represent a novel potential therapeutic target and prognostic marker for the treatment and diagnosis of HCC.

GOLPH2, a gene downstream of ras signaling, promotes the progression of pancreatic ductal adenocarcinoma.

Various studies have previously demonstrated that Golgi protein-73 (GOLPH2) is overexpressed in tumorigenesis, which has been observed in hepatocellular carcinoma and prostate cancer. However, the expression levels and specific functions of GOLPH2 in the progression of pancreatic cancer remain to be elucidated. The present study aimed to investigate the expression of GOLPH2 in pancreatic ductal adenocarcinoma (PDAC) tissues and examined the effects of GOLPH2 on the growth and migration of pancreatic cancer cells. In the present study, the mRNA levels of GOLPH2 in PDAC cancer tissues were examined using RT-qPCR. The effects of GOLPH2 on the growth and migration of cancer cells were examined using crystal violet and Boyden chamber assays. The study demonstrated that the expression of GOLPH2 mRNA and protein was elevated in PDAC clinical tissues. The growth and motility of the PDAC cells was enhanced following overexpression of GOLPH2, whereas downregulating the expression of GOLPH2 impaired the growth, motility and tumorigenesis. Furthermore, GOLPH2 was observed to interact with protein kinase B (Akt), which subsequently increased the activity of Akt. In addition, GOLPH2 was revealed as a downstream gene of Ras signaling and promoted the transformation of normal pancreatic cells. The results of the present study revealed the important functions of GOLPH2 in PDAC, and suggest that GOLPH2 may act as a promising therapeutic target for the treatment of PDAC in the future.

Clinical significance and expression of serum Golgi protein 73 in primary hepatocellular carcinoma

Golgi protein 73 (GP73) is a potential serum marker for the diagnosis of hepatocellular carcinoma (HCC). However, the diagnostic value of GP73 for HCC remains controversy, and little is known about the relationship between serum GP73 concentration and clinical characteristics of HCC. This study was designed to analyze the clinical values of GP73 in diagnosing HCC and the relationship between GP73 level and clinical characteristics in HCC patients. In this study, a total of 443 serum samples including 180 patients with HCC, 61 patients with liver cirrhosis (LC), 99 chronic hepatitis patients, and 103 healthy individuals were enrolled from November 2011 to April 2013. Enzyme-linked immunosorbent assay and chemiluminescent immunoassay were used to detect the serum level of GP73 and other biomarkers. GP73 level in HCC group was significantly higher than LC group, chronic hepatitis B group, and healthy control group. In HCC group, GP73 level significantly increased in patients with lymphatic metastasis; moreover, GP73 level in Child-Pugh Class B and C groups was statistically significantly higher than that in Child-Pugh Class A group (P < 0.05). The area under the receiver operating characteristic (AUROC) curve of GP73 and alpha-fetoprotein (AFP) was 0.840 and 0.718, respectively, when diagnosing HCC. Moreover, the AUROC curve by use of the combination of GP73 and AFP was 0.903. The differences among these three aspects were statistically significant (P < 0.05). GP73 was better than AFP for the diagnosis of HCC, and the expression of serum GP73 is related with the clinical characteristics of HCC patients.

The Clinical Significance of GP73 in Immunologically Mediated Chronic Liver Diseases: Experimental Data and Literature Review.

There is significant void in establishing validated non-invasive surrogate biomarkers of liver fibrosis/cirrhosis in chronic liver diseases (CLD). Golgi protein 73 (GP73) has been suggested as a potential serum marker for the diagnosis of hepatocellular carcinoma (HCC). However, significant background of cirrhosis could have accounted for the elevation of serum GP73 in HCC. In this study, we have taken advantage of a well-defined extensive cohort of 3044 patients with either compensated cirrhosis (n = 1247), decompensated cirrhosis (n = 841) or pre-cirrhotic CLD (n = 956) and our ability to quantify serum GP73 to define the potential of serum GP73 as a biomarker of liver cirrhosis/fibrosis in CLD. The diagnostic value of GP73 was compared with aspartate aminotransferase-to-platelet ratio index (APRI), fibrosis index based on four factors (FIB-4) and liver stiffness measurement (LSM). Immunohistochemical analysis was performed to measure hepatic GP73 expression. Receiver operating characteristic curve analysis demonstrated that serum GP73 had a good diagnostic potential for compensated cirrhosis regardless of etiology. The diagnostic performance of GP73 is better than APRI, FIB-4 and similar with LSM, especially in patients with severe inflammation, steatosis and cholestasis. Notably, in patients of autoimmune liver diseases, non-alcoholic fatty liver disease and viral hepatitis, serum GP73 also exhibited diagnostic value for advanced fibrosis as well as cirrhosis. Furthermore, there is also a gradual increase in GP73 expression with disease progression from mild fibrosis to cirrhosis. In conclusion, GP73 is an effective and reliable serological marker for the diagnosis of advanced fibrosis and prediction of appearance of cirrhosis.

Assessment of serum Golgi protein 73 as a biomarker for the diagnosis of significant fibrosis in patients with chronic HBV infection.

Transient elastography (TE) is accurate in staging fibrosis noninvasively. However, a reliable serum biomarker with comparable accuracy is also important, especially when TE is unreliable/unavailable. Therefore, we aimed to evaluate the diagnostic performance of serum Golgi protein 73 (GP73) for significant fibrosis in patients with chronic HBV infection. A total of 801 patients with chronic liver disease (CLD; 492 chronic HBV infection and 309 non-HBV liver disease) with liver biopsy performance were enrolled. Healthy controls (n=180) and hepatocellular carcinoma (HCC) patients (n=85) were included for comparisons. Liver biopsy was used as the reference method for fibrosis staging. Serum GP73 level was measured in duplicate in double-blind fashion. Serum GP73 was highest in HCC but also significantly higher in chronic hepatitis B than in healthy controls. The elevation of serum GP73 in non-HCC patients was significantly associated with the presence of significant fibrosis independently of ALT level, liver stiffness (LS) value, inflammation grade and other confounding factors. The diagnostic performance of serum GP73 was accurate in antiviral-naïve HBV patients (area under the receiver operating curve [AUROC], 0.76 95% CI: 0.72-0.81) but not in patients with ongoing antiviral treatment (AUROC, 0.60). The utility of serum GP73 was also confirmed in non-HBV CLD (AUROC, 0.80 95% CI: 0.75-0.85). Serum GP73 was comparable to LS (AUROC, 0.78 95% CI: 0.73-0.82) and significantly better than AST to platelet ratio index (APRI) (AUROC, 0.67 95% CI: 0.62-0.72) and FIB-4 (AUROC, 0.68 95% CI: 0.63-0.73). In conclusion, serum GP73 is an accurate serum marker for significant fibrosis in chronic HBV infection, with higher accuracy than APRI and FIB-4. Serum GP73 is potentially a complementary tool for TE when evaluating the necessity of antiviral treatment, particularly in patients without definite antiviral indication.