Golgi Protein 73 Research Articles

An electrochemical biosensor based on MoS2-PANi@Fc for the detection of Golgi protein 73

Golgi protein 73 (GP73) is highly expressed in hepatocellular carcinoma (HCC) and has been regarded as a sensitive serum biomarker for HCC diagnosis. Herein, an electrochemical biosensor for the determination of GP73 was constructed based on the molybdenum disulfide-polyaniline@ferrocene (MoS2-PANi@Fc) nanocomposites. The MoS2-PANi@Fc was prepared with large surface area and excellent electrical properties. One aptamer for GP73 (GP73Apt1) immobilized on MoS2-PANi@Fc by π-π stacking and metal ligand interactions was used as an electrochemical signal reporter probe by Fc oxidation. Another GP73 aptamer (GP73Apt2) was immobilized on the surface of gold nanoparticles electrodeposition into screen-printed carbon electrode (Au NPs/SPCE) to capture the target GP73. In the presence of GP73, Fc electrochemical signal recorded by differential pulse voltammetry (DPV) increased gradually. The preparation processes, mechanisms and optimal experiment conditions of electrochemical biosensor were studied by electron microscope imaging, spectral curves and electrochemical measurements. Under optimized experimental conditions, the aptasensor was demonstrated to be capable of detecting GP73 with a linear range of 0.001–100.0 ng mL−1 and a limit of detection (LOD) of 0.001 ng mL−1 (σ = 3). Stability, specificity and reproducibility were well demonstrated. These results may provide new insights for clinical detection of HCC.

Competitive electrochemical aptasensor for high sensitivity detection of liver cancer marker GP73 based on rGO-Fc-PANi nanocomposites

Golgi protein 73 (GP73) is a novel tumor marker in the early diagnosis and prognosis of hepatocellular carcinoma (HCC). Herein, a competitive electrochemical aptasensor for detecting GP73 was constructed using reduced graphene oxide-ferrocene-polyaniline nanocomposite (rGO-Fc-PANi) as the biosensing platform. The rGO-Fc-PANi had larger specific surface area, excellent conductivity and outstanding electroactive performance, which served as nanocarrier for GP73 aptamer (GP73Apt) binding and as redox nanoprobe for record electrical signal. Then, a complementary chain (cDNA) was fixed to the electrode by hybridization with GP73Apt. When GP73 was present, a competitive process happened among cDNA, GP73Apt and GP73, formed the GP73-GP73Apt stable chemical structure and made cDNA detach from the sensing electrode, resulting in enhancement of electrical signal. The difference in the corresponding peak current before and after the competition can be used to indicate the quantitative of GP73. Under optimal conditions, the DPV current response showed a good log-linear relationship with GP73 concentrations (0.001 ∼ 100.0 ng/mL) with a detection limit of 0.15 pg/mL (S/N = 3). It was successfully used for GP73 detection in human serum with RSDs ranging from 1.08 % to 6.96 %. Therefore, the aptasensor could provide an innovative technology platform and hold a great potential in clinical application.

Fluorescence/electrochemical dual-mode strategy for Golgi protein 73 detection based on molybdenum disulfide/ferrocene/palladium nanoparticles and nitrogen-doped graphene quantum dots.

Golgi protein 73 (GP73) is a new serum marker associated with early diagnosis and postoperative assessment of hepatocellular carcinoma (HCC). Herein, an electrochemical/fluorescence dual-signal biosensor was designed for determination of GP73 based on molybdenum disulfide/ferrocene/palladium nanoparticles (MoS2-Fc-PdNPs) and nitrogen-doped graphene quantum dots (NGQDs). GP73 aptamer (Apt) was labeled with NGQDs to form the NGQDs-Apt fluorescence probe. MoS2-Fc-PdNPs served not onlyas the fluorescence quencher but also as electrochemical enhancer. The sensing platform (NGQDs-Apt/MoS2-Fc-PdNPs) was formed based on the fluorescence resonance energy transfer (FRET) mechanism. In the presence of GP73, the specific binding of NGQDs-Apt to GP73 interrupted FRET, restoring the fluorescence of NGQDs-Apt at λex/em = 348/438nm and enhancing the oxidation current of Fc in MoS2-Fc-PdNPs at 0.04V through differential pulse voltammetry (DPV). Under the optimal conditions, the DPV current change and fluorescence recovery have a good linear relationship with GP73 concentration from 1.00 to 10.0ng/mL. The calibration equation for the fluorescence mode was Y1 = (0.0213 ± 0.00127)X + (0.0641 ± 0.00448) and LOD was 0.812ng/mL (S/N = 3). The calibration equation of the electrochemical mode was Y2 = (3.41 ± 0.111)X + (1.62 ± 0.731), and LOD of 0.0425ng/mL (S/N = 3). The RSDs of fluorescence mode and electrochemical mode after serum detection were 1.62 to 5.21% and 0.180 to 6.62%, respectively. By combining the electrochemical and fluorescence assay, more comprehensive and valuable information for GP73 was provided. Such dual-mode detection platform shows excellent reproducibility, stability, and selectivity and has great application potential.

Risk Factors for Early Recurrence After Radical Resection of Hepatocellular Carcinoma Based on Preoperative Contrast-Enhanced Ultrasound and Clinical Features.

To investigate risk factors for the early recurrence (ER) of hepatocellular carcinoma (HCC) after radical resection based on preoperative contrast-enhanced ultrasound (CEUS) and clinical features to provide guidance for clinical treatment. The retrospective analysis selected 130 HCC patients who underwent radical tumor resection from October 2019 to November 2021. All patients underwent preoperative routine ultrasound examination and CEUS, and the pathology was confirmed as HCC after surgery. The patients were divided into two groups based on whether there is an ER, namely the ER group and the non-ER group. The general clinical, routine and CEUS data of patients were collected, and the factors were selected by using the least absolute shrinkage and selection operator (LASSO) regression. Multivariate logistic regression was used to screen the independent influencing factors of ER. Then a nomogram model was established to predict the risk of ER, and the application value of nomogram through internal validation was evaluated. Multivariate logistic regression identified several independent factors influencing ER after radical HCC resection. Significant factors included early wash-out phase (95%CI = 0.003-0.206, P = 0.001), liver cirrhosis (95%CI = 2.835-221.224, P = 0.004), incomplete envelope (95%CI = 5.247-1056.130,P = 0.001), multiple lesions (95%CI = 1.110-135.424,P = 0.041), Albumin <40 g/L (95%CI = 2.496-127.223,P = 0.004), and Golgi Protein 73 (GP73) ≥ 85 ng/mL (95%CI = 1.594-30.002, P = 0.010), with all P-values <0.05. The nomogram prediction model constructed based on the results of multivariate logistic regression, demonstrated a ROC curve AUC of 0.879, a sensitivity of 93.5%, a specificity of 66.7%, and a C-index of 0.602, indicating superior diagnostic efficiency compared to independent influencing factors. The ER nomogram prediction model confirmed good discrimination and calibration in internal validation. The CEUS-Clinical combined model effectively monitors the risk of ER in high-risk populations following radical resection of HCC, timely interventions to improve patient prognosis.

Golgi Protein 73 Promotes Angiogenesis in Hepatocellular Carcinoma.

Golgi protein 73 (GP73), a resident protein of the Golgi apparatus, is notably elevated in hepatocellular carcinoma (HCC). While its critical role in remodeling the tumor microenvironment (TME) is recognized, the intricate mechanisms are not fully understood. This study reveals that GP73 in HCC cells interacts with prolyl hydroxylase-2 (PHD-2) in a competitive manner, thereby impeding the hydroxylation of hypoxia-induced factor-1α (HIF-1α). The effect above promotes the production and secretion of vascular endothelial growth factor A (VEGFA). Moreover, exosomal GP73 derived from HCC cells can be internalized by human umbilical vein endothelial cells (HUVECs) and competitively interact with HECTD1, an E3 ubiquitin ligase targeting growth factor receptor-bound protein 2 (GRB2). This interaction stabilizes GRB2, thereby activating the Ras-mitogen-activated protein kinase (MAPK) signaling pathway. Consequently, escalated levels of GP73 intensify VEGF production in HCC cells and potentiate mitogenic signaling in vascular endothelial cells, fostering angiogenesis in the TME. Our findings propose that GP73 might serve as a novel target for anti-angiogenic therapy in HCC.

Novel serum biomarker of Golgi protein 73 for the diagnosis of clinically significant portal hypertension in patients with compensated cirrhosis.

Hepatic venous pressure gradient (HVPG) is the gold standard for evaluating clinically significant portal hypertension (CSPH). However, reliable noninvasive methods are limited. Our study aims to investigate the diagnostic value of serum Golgi protein 73 (GP73) for CSPH in patients with compensated cirrhosis. The study enrolled 262 consecutive patients with compensated cirrhosis from three centers in China from February 2021 to September 2023, who underwent both serum GP73 tests and HVPG measurements. CSPH was defined as HVPG ≥ 10 mmHg. Diagnostic accuracy was evaluated using the areas under the receiver operating characteristic curve (AUC). The prevalence of CSPH was 56.9% (n = 149). There were significant differences between the CSPH and non-CSPH groups in the median serum GP73 level (126.8 vs. 73.1 ng/mL, p < 0.001). GP73 level showed a significant positive linear correlation with HVPG (r = 0.459, p < 0.001). The AUC for the diagnosis of CSPH using serum GP73 alone was 0.75 (95% confidence interval [CI] 0.68-0.81). Multivariate logistic regression analysis determined that the levels of GP73, platelets and international normalized ratio were independently associated with CSPH. The combination of these three markers was termed "IP73" score with an AUC value of 0.85 (95% CI 0.80-0.89) for CSPH. Using 0 as a cut-off value, the specificity and sensitivity of IP73 score were 77.9% and 81.9%, respectively. The IP73 score offers a novel, simple and noninvasive method of assessing CSPH in patients with compensated cirrhosis. A cut-off value of the IP73 score at 0 can distinguish patients with or without CSPH.

The Relationship between Golgi Protein 73, Alpha-Fetoprotein, Liver Function Indicators, and Traditional Chinese Medicine Syndrome Types of Primary Liver Cancer

Abstract Objective Our objective was to analyze the correlation between Golgi protein 73 (GP73), alpha-fetoprotein (AFP), liver function indicators, and traditional Chinese medicine (TCM) syndrome types of primary liver cancer (hereinafter referred to as “liver cancer”). Methods In total, 156 liver cancer patients (liver cancer group) and 52 healthy individuals (health group) were selected as the research subjects to detect their GP73, AFP expression, and liver function-related indicators. The obtained data were statistically analyzed using SPSS 21.0 software. Results (1) The positive expression rate of GP73 in the liver cancer group was 50%; the positive expression rates of qi stagnation and blood stasis syndrome, heat toxin in liver and gallbladder syndrome, and yin deficiency of liver and kidney syndrome were 37.9, 54.3, and 59.6%, respectively. There was no statistically significant difference between the groups (p &gt; 0.05). The positive expression rate of AFP was 50%. The positive expression rates of qi stagnation and blood stasis syndrome, heat-toxin in liver and gallbladder syndrome, and yin deficiency of liver and kidney syndrome were 41.7, 54.3, and 59.6%, respectively. There was a statistically significant difference between the groups (p &lt; 0.05). (2) The GP73 levels of patients with different syndrome types in the liver cancer group were ranked from high to low as yin deficiency of liver and kidney syndrome, heat toxin in liver and gallbladder syndrome, and qi stagnation and blood stasis syndrome. The differences between the groups were statistically significant (p &lt; 0.05). The AFP levels of patients with different syndrome types in the liver cancer group were ranked from high to low as heat toxin in liver and gallbladder syndrome, yin deficiency of liver and kidney syndrome, and qi stagnation and blood stasis syndrome. There was no statistically significant difference between the groups (p &gt; 0.05). (3) Analysis of liver function indicators in the liver cancer group: the alanine transaminase (ALT) levels of patients with different syndrome types were in descending order from high to low, including yin deficiency of liver and kidney syndrome, heat toxin in liver and gallbladder syndrome, and qi stagnation and blood stasis syndrome. The differences between groups were statistically significant (p &lt; 0.05). The aspartate aminotransferase (AST) levels of patients with different syndrome types were ranked from high to low as follows: heat toxin in liver and gallbladder syndrome, yin deficiency of liver and kidney syndrome, and qi stagnation and blood stasis syndrome. The difference between groups was statistically significant (p &lt; 0.05). The levels of albumin (ALB) in patients with different syndrome types were ranked from high to low, including heat toxin in liver and gallbladder syndrome, qi stagnation and blood stasis syndrome, and yin deficiency of liver and kidney syndrome. The differences between groups were statistically significant (p &lt; 0.05). Conclusion GP73 and indicators such as ALT, AST, and ALB are of great significance in the diagnosis of TCM syndrome differentiation and classification of liver cancer patients.

Systematic review: Glycomics as diagnostic markers for hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the most prevalent primary liver cancer with one of the highest cancer-related mortality rates worldwide. Early diagnosis is crucial for improving the therapeutic options and reducing the disease-related mortality. To investigate serum N-glycomics as diagnostic markers for HCC. We performed a comprehensive search in PubMed, EMBASE, Web of Science and Scopus through August 17, 2023. Eligible studies assessed the potential use of serum N-glycomics as diagnostic biomarkers for HCC. Study selection, data extraction and quality assessment were performed by two independent reviewers. Of the 48 articles included, 11 evaluated the utility of N-glycomics for the diagnosis of HCC in whole serum while the remaining articles focused on specific protein glycoforms or protein levels. Of these specific proteins, haptoglobin, alpha-fetoprotein (AFP), kininogen (Kin), α-1-antitrypsin and Golgi protein 73 (GP73) were the most frequently studied. Increased levels of fucosylation and branching presented as the most prevalent post-translational modifications of glycoproteins in patients with HCC compared to controls. Notably, glycomics-based biomarkers may provide a clinical benefit for the diagnosis of early HCC, as several algorithms achieved AUCs between 0.92-0.97. However, these were based on single studies with limited sample sizes and should therefore be validated. Alterations in serum N-glycomics, characterised by increased levels of fucosylation and branching, have potential as diagnostic biomarkers for HCC. Optimisation of study design, patient selection and analysing techniques are needed before clinical implementation will be possible.

Clinical utility of biomarkers of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the most common forms of cancer significantly affecting the mortality and morbidity rates. The increasing incidence of HCC is a great concern across the globe. The current methods of HCC screening, detection and diagnosis depend mainly on imaging techniques. However, biomarkers represent a relatively easy and noninvasive way to detect and estimate the disease prognosis. New potential biomarkers such as α-fetoprotein (AFP), des‑γ‑carboxyprothrombin (DCP), α-fetoprotein L3 (AFP-L3), glypican 3 (GCP3), micro-RNA, and Golgi-protein 73 (GP73) are being used more often in the diagnosis and prognosis of HCC. The lack of prudent diagnostic measures makes early detection of HCC nearly impossible. The use of biomarkers to detect cancer has helped to screen for the disease. However, the most commonly used biomarkers for HCC have inadequate performance characteristics. Despite numerous efforts to identify molecules as potential biomarkers, there is no single ideal marker for HCC. In this paper the main biomarkers for the surveillance, diagnosis and prognosis of HCC are reviewed. The advantages and limitations of these biomarkers are summarized, and the future development directions are proposed (Tab. 1, Ref. 30). Keywords: hepatocellular carcinoma, biomarkers, AFP, DCP, diagnosis.

Golgi Protein 73 Promotes LPS-Induced Cardiac Dysfunction via Mediating Myocardial Apoptosis and Autophagy.

Sepsis-induced cardiac dysfunction represents a major cause of high mortality in intensive care units with limited therapeutic options. Golgi protein 73 (GP73) has been implicated in various diseases. However, the role of GP73 in lipopolysaccharide (LPS)-induced cardiac dysfunction is unclear. In this study, we established a sepsis-induced cardiac dysfunction model by LPS administration in wild-type and GP73 knockout ( GP73-/- ) mice. We found that GP73 was increased in LPS-treated mouse hearts and LPS-cultured neonatal rat cardiomyocytes (NRCMs). Knockout of GP73 alleviated myocardial injury and improved cardiac dysfunction. Moreover, depletion of GP73 in NRCMs relieved LPS-induced cardiomyocyte apoptosis and activated myocardial autophagy. Therefore, GP73 is a negative regulator in LPS-induced cardiac dysfunction by promoting cardiomyocyte apoptosis and inhibiting cardiomyocyte autophagy.

Diagnostic Role of Serum Golgi Protein 73 as a Biomarker for the Assessment of Significant Hepatic Fibrosis in Patients with Chronic Hepatitis B Infection

Abstract Background Significant fibrosis is the hallmark of progressive nature of chronic HBV infection. Therefore, it is fundamentally important to detect significant fibrosis accurately for decision on subsequent clinical management. Liver stiffness (LS) determined with Transient elastography (TE) and non-invasive indirect serum biomarkers (APRI score and FIB-4 Index) are most promising approaches in non- invasively evaluating significant liver fibrosis and minimizing the need of invasive liver biopsy. A recently introduced fibrosis biomarker in chronic liver diseases is Serum Golgi protein 73 (GP73). Aim The current study aimed at assessing the diagnostic accuracy of serum GP73 for significant fibrosis in antiviral-naïve HBV patients. Methods Forty patients who have never been treated for HBV infection were enrolled. They were subjected to full history, clinical, laboratory assessment and imaging by abdominal ultrasound. Serum Golgi protein 73 level were assessed for all patients and compared with APRI score, FIB-4 index results. Results Out of 40 patients who were enrolled, 65% % were males. The mean age was 43.78±11.58 years. 11 patients (27.5%) had significant liver fibrosis (≥ F2) and 29 patients (72.5%) had “No or Mild Fibrosis (&amp;lt;F2) as evidenced by both APRI and FIB-4. Our study showed Statistically significant correlation between APRI score and FIB-4 Index with age of the patients, haemoglobin level, Platelets, albumin, AST level, ALT level, INR and Direct bilirubin levels with p value &amp;lt;0.001 for the age, AST, ALT, Platelets and Albumin, with p value &amp;lt;0.015 for haemoglobin and Direct bilirubin and with p value &amp;lt;0.005 for INR By using Pearson Correlation Coefficient. Serum biomarker GP 73 showed statistically significant correlation with Age in years (P &amp;lt;0.005), AST level (P &amp;lt;0.017), ALT level (P &amp;lt;0.022) and Platelets (P &amp;lt;0.002) and statistically insignificant correlation with Haemoglobin, albumin level, INR, and direct bilirubin level. Conclusions Noninvasive simple biomarkers FIB-4, APRI and measurements of GP 73 can be used as good predictor of liver fibrosis in antiviral-naïve chronic HBV patients which can minimize the need for invasive liver biopsy in prediction of significant hepatic fibrosis.

Circulating biomarkers of mortality prediction in patients undergoing liver transplantation due to hepatocellular carcinoma

There are different macromorphological factors obtained prior to liver transplantation (LT) to predict the prognosis of hepatocellular carcinoma (HCC) patients undergoing LT. The use of blood biomarkers could help improve the prognosis prediction of these patients. Blood levels of alpha-fetoprotein (AFP) are the first and most studied prognostic blood biomarkers of HCC patients undergoing LT. This review is to summarize the evidence of prognostic blood biomarkers for HCC patients undergoing LT. A higher mortality rate has been found with high blood levels of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), C-reactive protein (CRP), albumin-bilirubin (ALBI) score, des-gamma-carboxy prothrombin (DCP), lactate dehydrogenase (LDH), gamma glutamyl transpeptidase (GGT), fibrinogen, vascular endothelial growth factor (VEGF), homocysteine, Golgi protein 73 (GP73), substance P, soluble CD40 ligand (sCD40L), caspase-cleaved cytokeratin (CCCK)-18, caspase-3, malondialdehyde and oxidized guanine species (OGS). A higher mortality rate has been found with low blood levels of lymphocyte-to-monocyte ratio (LMR), PD-L1, Galectin-9, total antioxidant capacity (TAC) and melatonin. Moreover, some studies with small sample sizes associate blood levels of metabolites and microRNAs (MIRs) with the prognosis of HCC patients undergoing LT. More research is warranted to determine the possible utility of these biomarkers to predict the prognosis of HCC.

An ultrasensitive label-free electrochemical aptasensing platform for Golgi protein-73 detection based on RGO-Fc-Mn3O4 nanocomposites

Golgi protein-73(GP73) is one of the most common biomarkers with outstanding sensitivity and specificity in the diagnosis of hepatocellular carcinoma. Herein an ultrasensitive label-free electrochemical aptasensing platform was constructed for GP73 detection based on reduced graphene oxide-ferrocene formic acid-tripterythrine tetroxide nanocomposites (RGO-Fc-Mn3O4) and GP73 aptamer (GP73Apt). Gold@poly-o-phenylenediamine (Au@PoPD) was electrodeposited on the surface of screen-printed electrode (SPE) as the conductive substrate. RGO-Fc-Mn3O4 was then drop-coated on Au@PoPD/SPE as a signal probe to generate measurable redox peaks due to the electroactivity of Fc in RGO-Fc-Mn3O4. GP73Apt was anchored on the surface of RGO-Fc-Mn3O4 NPs/Au@PoPD/SPE to constitute an electrochemical aptasensing biosensor. When GP73 was captured via the specific affinity of GP73Apt and formed GP73-GP73Apt complex onto the aptasensing platform, the formation GP73-GP73Apt complex impeded the electron transfer on the electrode interface, resulting in a decrease in the peak current recorded by differential pulse voltammetry method. Thus, GP73 can be detected by measuring the change of Fc redox peak current in RGO-Fc-Mn3O4. Log-linear calibration curve for GP73 concentration (0.01–1000 ng/mL) was obtained with good correlation coefficients of 0.99485 and a lower limit of detection of 0.01 ng/mL. The human serum samples were tested by direct detection method, and the relative error and relative standard deviation are 4.21–9.87% and 3.28–9.40%, respectively. All these results demonstrate that the proposed aptasensor would be a promising tool for clinical analysis of GP73 in the diagnosis of hepatocellular carcinoma.

A novel fluorescent strategy for Golgi protein 73 determination based on aptamer/nitrogen-doped graphene quantum dots/molybdenum disulfide @ reduced graphene oxide nanosheets.

The effective detection of biomarkers associated with hepatocellular carcinoma (HCC) is of great importance. Golgi protein 73 (GP73), a serum biomarker of HCC, has better diagnostic value than Alpha-fetoprotein (AFP) has been reported. In this paper, highly accurate fluorescence sensing platform for detecting GP73 was constructed based on fluorescence resonance energy transfer (FRET), in which nitrogen-doped graphene quantum dots (NGQDs) labelling with GP73 aptamer (GP73Apt) was used as fluorescence probe, and molybdenum disulfide @ reduced graphene oxide (MoS2@RGO) nanosheets was used as fluorescent receptors. MoS2@RGO nanosheets can quench the fluorescence of NGQDs-GP73Apt owing to FRET mechanisms. In the presence of GP73, the NGQDs-GP73Apt specifically bound with GP73 to from the deployable structures, making NGQDs-GP73Apt far away from MoS2@RGO nanosheets, blocking the FRET process, resulting in fluorescence recovery of NGQDs-GP73Apt. Under optimal conditions, the recovery intensity of fluorescence in the detection system is linearly related to the concentration of GP73 in the range of 5ng/mL - 100ng/mL and the limit of detection is 4.54ng/mL (S/N=3). Moreover, detection of GP73 was performed in human serum samples with good recovery (97.21-100.83%). This platform provides a feasible method for the early diagnosis of HCC, and can be easily extended to the detection of other biomarkers.

Whether the Golgi protein 73 could be a diagnostic serological marker in hepatocellular carcinoma: a meta analysis

BackgroundThe Value of Golgi protein 73 (GP73) in the diagnosis of Hepatocellular carcinoma (HCC) remains controversial, especially in its differentiation between HCC and cirrhosis. Besides, some papers showed that GP73 levels are correlated with liver fibrosis. This study conducts a meta-analysis to evaluate the value of GP73 in diagnosing HCC and differential diagnosing HCC from liver cirrhosis.Methods36 studies with a sample size of 8314 cases concerning the accuracy of GP73 in the diagnosis of HCC were selected through a systematic review. Seven of these studies included a total of 438 HCC samples and 426 cirrhosis samples and calculated the sensitivity and specificity of GP73 for differential diagnosing HCC from cirrhosis. QUADAS (quality assessment of diagnostic accuracy studies) was used to evaluate the quality of literature. Statistical analyses were performed using StataSE16 software.ResultsThe pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio and the area under the curve were 0.79(95%CI 0.74–0.83),0.85(95%CI 0.80–0.89),5.4(95%CI 3.8–7.5), 0.25(95%CI 0.20–0.31), 22(95%CI 13–35), and 0.88 for GP73 diagnosing HCC;0.74(95%CI 0.64–0.81),0.70(95%CI 0.49–0.85),2.40(95%CI 1.3–4.7),0.38(95%CI 0.23–0.61),6(95%CI 2–19), and 0.78 for GP73 differential diagnosing HCC from liver cirrhosis.ConclusionThe results suggest that GP73 has a high diagnostic value for HCC and a moderate value for differential diagnosis of HCC from liver cirrhosis.

GP73 blockade alleviates abnormal glucose homeostasis in diabetic mice.

Golgi protein 73 (GP73), also called Golgi membrane protein 1 (GOLM1), is a resident Golgi type II transmembrane protein and is considered as a serum marker for the detection of a variety of cancers. A recent work revealed the role of the secreted GP73 in stimulating liver glucose production and systemic glucose homeostasis. Since exaggerated hepatic glucose production plays a key role in the pathogenesis of type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM), GP73 may thus represent a potential therapeutic target for treating diabetic patients with pathologically elevated levels. Here, in this study, we found that the circulating GP73 levels were significantly elevated in T2DM and positively correlated with hemoglobin A1c. Notably, the aberrantly upregulated GP73 levels were indispensable for the enhanced protein kinase A signaling pathway associated with diabetes. In diet-induced obese mouse model, GP73 siRNA primarily targeting liver tissue was potently effective in alleviating abnormal glucose metabolism. Ablation of GP73 from whole animals also exerted a profound glucose-lowering effect. Importantly, neutralizing circulating GP73 improved glucose metabolism in streptozotocin (STZ) and high-fat diet/STZ-induced diabetic mice. We thus concluded that GP73 was a feasible therapeutic target for the treatment of diabetes.

Glypican-3, Vascular Endothelial Growth Factor and Golgi Protein-73 for Differentiation between Liver Cirrhosis and Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) accounts for more than 80% of primary liver cancers. Moreover, in the next 10 years, more than one million patients are expected to die from liver cancer as estimated by the World Health Organization. The aim of the present study is to evaluate the clinical utility of using Glypican (GPC3), Vascular endothelial growth factor (VEGF) and Golgi protein 73 (GP73) in serum by Enzyme-Linked Immunosorbent Assay (ELISA) and by Real-Time Polymerase Chain Reaction (RT-PCR), as diagnostic markers to differentiate HCC from cirrhotic liver disease. A total of 50 patients with histologically-proven HCC, 50 liver cirrhosis patients and 20 healthy volunteers as controls were enrolled in this study, blood samples were obtained from each patient. Expression of the studied biomarkers was evaluated by ELISA and Real-Time PCR. Statistical analysis of RT-PCR results showed that the expression of GPC3, VEGF and GP73 in serum of patients with HCC was significant (P value < 0.001, 0.01, and < 0.001) respectively and increased when compared to the cirrhotic group. Furthermore, the serum protein levels of GPC3 and VEGF in HCC and cirrhotic patients were significant when compared to the control group. While no significance was found between HCC and cirrhotic group. The serum protein level of GP73 was significantly increased in HCC and cirrhosis groups compared to the control group (P value < 0.001). Moreover, a significant increase was evident in HCC group compared to cirrhotic group (P value < 0.001). The results of the present study showed that the combination of VEGF and GP73 could discriminate HCC from cirrhosis. GPC3, VEGF and GP73 are reliable biomarkers for diagnosis of HCC. The serum level of GP73 is a potential screening marker for discriminating HCC from liver cirrhosis.

Diagnostic value of novel hepatic fibrosis markers in assessing cirrhosis in patients with chronic hepatitis C

Objective: To investigate the efficacy of chitinase-3-like protein 1 (CHI3L1) and Golgi protein 73 (GP73) in the diagnosis of cirrhosis and the dynamic changes of CHI3L1 and GP73 after HCV clearance in patients with chronic hepatitis C (CHC) treated with direct-acting antiviral drugs (DAAs). The comparison of continuous variables of normal distribution were statistically analyzed by ANOVA and t-test. The comparison of continuous variables of non-normal distribution were statistically analyzed by rank sum test. The categorical variables were statistically analyzed by Fisher's exact test and χ(2) test. Correlation analysis was performed using Spearman correlation analysis. Methods: Data of 105 patients with CHC diagnosed from January 2017 to December 2019 were collected. The receiver operating characteristic curve (ROC curve) was plotted to study the efficacy of serum CHI3L1 and GP73 for the diagnosis of cirrhosis. Friedman test was used to compare CHI3L1 and GP73 change characteristics. Results: The areas under the ROC curve for CHI3L1 and GP73 in the diagnosis of cirrhosis at baseline were 0.939 and 0.839, respectively. Serum levels of CHI3L1 and GP73 in the DAAs group decreased significantly at the end of treatment compared with baseline [123.79 (60.25, 178.80) ng/ml vs. 118.20 (47.68, 151.36) ng/ml, P = 0.001; 105.73 (85.05, 130.69) ng/ml vs. 95.52 (69.52, 118.97) ng/ml, P = 0.001]. Serum CHI3L1 and GP73 in the pegylated interferon combined with ribavirin (PR) group were significantly lower at the end of 24 weeks of treatment than the baseline [89.15 (39.15, 149.74) ng/ml vs. 69.98 (20.52, 71.96) ng/ml, P < 0.05; 85.07 (60.07, 121) ng/ml vs. 54.17 (29.17, 78.65) ng/ml, P < 0.05]. Conclusion: CHI3L1 and GP73 are sensitive serological markers that can be used to monitor the fibrosis prognosis in CHC patients during treatment and after obtaining a sustained virological response. Serum CHI3L1 and GP73 levels in the DAAs group decreased earlier than those in the PR group, and the serum CHI3L1 levels in the untreated group increased compared with the baseline at about two years of follow-up.

GP73 is a promising indicator in HIV diagnosis and treatment: a one-year follow-up study

Golgi protein 73 (GP73) has been recognized as a biomarker for evaluating liver diseases, although the serum profile of patients with HIV remains unclear. This study was designed to investigate the diagnostic values of serum GP73 in patients with HIV. A total of 92 patients with HIV and 60 healthy participants were selected, and serum samples were collected; 51 of 92 patients were followed up and all indicators were re-tested after 1 year. Patients with HIV had significantly lower GP73 concentration, lower viral load, and higher CD4+ T cell counts after antiretroviral treatment. A significant correlation between the changes of GP73 level and CD4+ T cell count was observed. The CD4+ T cell count was significantly correlated with the glycosylated GP73 level. The area under the ROC curve (AUC) of GP73 to predict negative viral load-negative conversion alone was 0.705. When the cut-off value was set at 146.7 ng/mL, the sensitivity and specificity were 73% and 70% respectively. These results indicate that serum GP73 may have predictive ability for negative viral load-negative conversion.

A study on the diagnostic value of GP73 in liver fibrosis among patients with chronic liver disease

Objective: This study aimed to evaluate the diagnostic value of serum Golgi protein 73(GP73) alone and GP73 combined with liver stiffness measurement (LSM), aspartate aminotransferase/platelet ratio index (APRI), and 4-factor-based fibrosis index (FIB4) in diagnosing liver fibrosis in patients with chronic liver disease of different etiologies. Methods: A diagnostic test. A total of 68 patients who underwent liver biopsy in the Department of Traditional and Western Medical Hepatology of the Third Hospital of Hebei Medical University from October 2019 to December 2020 were selected to detect serum GP73 levels. iLivTouch was used to assess liver stiffness measurement (LSM). In addition, serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), total bilirubin (TBil), direct bilirubin (DBil), triglyceride (TG), total cholesterol (TC), low-density lipoprotein (LDL) levels, and peripheral platelet (PLT) counts were assayed. The correlation between GP73 and the above indexes was assessed, and APRI and FIB-4 were calculated. SPSS 21.0 statistical software was used for statistical analysis. The area under the receiver operating characteristic curve was calculated to evaluate diagnostic efficacy of GP73 in identifying hepatic fibrosis stages. Furthermore, the difference between GP73 and liver stiffness, as well as APRI and FIB4 in diagnosing significant fibrosis was assessed. Results: Based on liver biopsy, 13, 18, 17, and 20 cases were diagnosed as stages S0-1, S2, S3, and S4, respectively. The AUC of GP73 diagnosing hepatic fibrosis stage S≥3 and S=4 were 0.806 and 0.844 at cut-off points of 2.06 and 3.27 μg/L, and the sensitivity and specificity were 93.5%, 61.5%, 90.0%, 70.3%, respectively. In addition, GP73 levels were positively correlated with the degree of liver fibrosis (r=0.547, P<0.001). Conclusions: The efficacy of serum GP73 level in diagnosing the degree of liver fibrosis in patients with chronic liver disease from different causes was significantly higher than that of APRI, FIB4, and LSM. The combination of GP73 and FIB4 can further improve the accuracy of diagnosis of liver fibrosis staging S≥3 and S=4, which is a reliable serological marker for the diagnosis of fibrosis in patients with chronic liver disease.