Role of serum Golgi protein 73 in nonalcoholic fatty liver disease / 临床肝胆病杂志

Golgi protein 73 (GP73) is a Golgi transmembrane protein that can be released into blood by cleavage. An increasing number of studies have shown that the increase in serum GP73 is closely associated with the development and progression of nonalcoholic fatty liver disease (NAFLD) and serum GP73 is expected to be used as a potential serological marker for the diagnosis and assessment of NAFLD. This article reviews the research advances in serum GP73 in NAFLD and analyzes its potential mechanism of action, so as to provide new options for the therapeutic targets of NAFLD.

Diagnostic value of novel hepatic fibrosis markers in assessing cirrhosis in patients with chronic hepatitis C / 中华肝脏病杂志

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 level in patients with chronic hepatitis B: Relationship with liver biopsy, levels of ALT, AST and HBV DNA

Background/Aims: In this study, we investigated the Golgi protein 73 (GP73) level in Hepatitis B and determined the correlation between Hepatitis B virus (HBV) DNA, alanine aminotransferase (ALT), aspartate aminotransferase (AST) levels, and liver histopathology. Materials and Methods: GP73 levels were estimated by enzyme-linked immunosorbent assay in serum samples from patients. Liver biopsy specimens were examined by the same pathologist. Results: This study included a total of 127 patients who underwent liver biopsy. Of patients, 85% were HBeAg negative. HBV DNA level was median 134667 IU/mL (2247–170000000 IU/mL), Liver biopsy results revealed a mean Histological Activity Index (HAI) grade of 7.7 ± 3.4 and a mean fibrosis stage of 2.25 ± 1.06 gr/dL. GP73 was as follows: a mean of 14.8 ± 7.9 ng/mL and a median of 12.9 (4.8–50.1) ng/mL. A weak correlation between GP73 level and AST (r = 0.236, P = 0.11), fibrosis stage (r = 0.287, P = 0.002), and HAI grade (r = 0.218, P = 0.016) was noted. No statistically significant correlation was detected between GP73 and ALT (r = 0.16, P = 0.08), HBV DNA (r = 0.13, P = 0.08). Conclusion: Although recent studies revealed a strong correlation and increased GP73 levels in accordance with HAI scores and the fibrosis grade of liver, we detected a weak correlation between serum GP73 levels and HAI scores, fibrosis stage, and AST. This may be due to the insufficient number of patients with higher HAI grading and fibrosis staging in our study. Therefore, we concluded that, in cases of low-moderate fibrosis and HAI grading, GP73 seemed not to be useful and a reliable marker to replace liver biopsy.

Changes of serum Golgi protein 73 expression and its clinical significance in breast cancer patients before and after radiotherapy / 中华内分泌外科杂志

Objective:To investigate the changes of serum Golgi protein 73 (GP73) expression and its clinical significance in breast cancer patients before and after radiotherapy.Methods:A total of 135 patients with primary breast cancer who were diagnosed and treated in Qingdao Hospital Affiliated to Shandong First Medical University Hospital from Aug. 2016 to Dec. 2017 were selected and received standard radiotherapy after surgery. Enzyme-linked immunosorbent assay (ELISA) was used to determine the content of GP73 in the serum of patients before and after radiotherapy, and the differences in the expression levels of GP73 before and after radiotherapy in patients with different molecular phenotypes, tumor stages, and pathological types were compared. Association between the expression of serum GP73 and clinical outcome before and after radiotherapy was analyzed.Results:The expression of GP73 in breast cancer patients was (117.69±33.57) mg/L before radiotherapy and (101.88±30.92) mg/L after radiotherapy, and the difference was statistically significant ( t=4.025, P<0.001) . Different molecular phenotypes were stratified and found that the expression of serum GP73 in patients with luminal A, luminal B, HER-2 overexpression, and triple negative after radiotherapy decreased compared with those before radiotherapy, but only the HER-2 overexpression type had statistically significant difference between before and after radiotherapy ( P<0.05) . Stratification according to different tumor stages showed that the expression of serum GP73 in patients with stage I, II, III and IV after radiotherapy was lower than that before radiotherapy, but only the patients with stage II, stage III, and stage IV were compared before and after radiotherapy, and the difference was statistically significant ( P<0.05) . Stratification according to different pathological types showed that the expression of serum GP73 in patients with invasive ductal carcinoma before and after radiotherapy was significantly lower in patients with invasive lobular carcinoma ( P<0.05) . In addition, the 1-year survival rate of the descending group was significantly higher than that of the ascending group, while the local recurrence rate and the occurrence of distant metastasis were significantly lower than those of the ascending group, and the difference was statistically significant ( P<0.05) . Conclusions:The expression level of serum GP73 in breast cancer patients after radiotherapy is significantly higher than that before radiotherapy, and it has a certain relationship with molecular phenotype, tumor stage, and pathological type. At the same time, the increase in serum GP73 expression after radiotherapy may be detrimental to the clinical outcome of patients.

Clinical significance of Golgi protein 73 in liver cirrhosis and its relationship with radiological parameters / 中国辐射卫生

Objective To explore the clinical significance of serum Golgi protein 73 (GP73) in liver cirrhosis and its association with radiological parameters. Methods We included 177 patients with liver cirrhosis and 61 patients with chronic hepatitis admitted to The First Hospital of Jilin University from January 2016 to December 2018, with 70 healthy subjects who underwent physical examination during the same period as the control. We compared GP73, alanine transaminase (ALT), aspartate transaminase (AST), albumin (ALB), total bilirubin (TBIL), prothrombin time (PT), and main portal vein diameter between the patients with liver cirrhosis, patients with chronic hepatitis, and healthy subjects. The GP73 level was further compared between liver cirrhosis subgroups by various classification methods. The correlation between GP73 and ALT, AST, ALB, TBIL, PT, and main portal vein diameter was analyzed. Results The GP73 level was significantly higher in the liver cirrhosis group than in the chronic hepatitis group and the healthy control group (P < 0.001). Patients with decompensated cirrhosis had a significantly higher serum GP73 level than those with compensated cirrhosis (P < 0.001). The serum GP73 levels in the Child-Pugh B and C cirrhosis subgroups were significantly higher than that in the Child-Pugh A cirrhosis subgroup (P < 0.05). In the liver cirrhosis group, the GP73 level was positively correlated with AST, ALT, TBIL, PT, and main portal vein diameter, while negatively correlated with ALB. Conclusion Serum GP73 is significantly increased in patients with liver cirrhosis, which is closely related to liver injury indicators. Serum GP73 shows important clinical value for the early diagnosis and prognosis assessment of liver cirrhosis.

Research progress in prognostic biomarkers of liver failure / 中国综合临床

Liver failure is a group of serious clinical syndrome, which develops rapidly and has a dangerous prognosis.In recent years, there are many biomarkers to evaluate the prognosis of patients with liver failure at home and abroad, such as neutrophil/lymphocyte ratio, alpha fetoprotein, galactose lectin-3, osteopontin, Golgi protein 73, human β - defensin-1, etc.these biomarkers are of great significance for early identification of patients with liver failure, accurate evaluation of their prognosis, and formulation of effective treatment plan.

Establishment and preliminary application of serum Golgi protein 73 based noninvasive diagnostic model for compensated stage hepatitis B cirrhosis / 中华肝脏病杂志

Objective@#To establish and evaluate diagnostic efficacy and applicability of serum Golgi protein (GP) 73 based non-invasive diagnostic model with other conventional serological indicators for compensated stage hepatitis B cirrhosis.@*Methods@#666 cases with chronic hepatitis B (CHB) who had visited to the Fifth Medical Center of People’s Liberation Army General Hospital from January 2010 to December 2017 were selected as the study subjects, and were classified according to compensated stage cirrhosis into clinical and pathological diagnosis group based on whether or not the liver histological examination was performed. A diagnostic model of compensated stage hepatitis B cirrhosis in the clinical diagnosis group was established. The current clinically used diagnostic model of liver cirrhosis, aspartate aminotransferase/platelet ratio index (APRI), fibrosis index (FIB)-4 and liver stiffness measurement (LSM) were compared. Eventually, the diagnostic model was verified step by step by pathological diagnosis group.@*Results@#The area under the receiver operating characteristic curve (AUC) of GP73 and APRI, FIB-4, and LSM for cirrhosis patients in the clinical diagnosis group were 0.842, 0.857, 0.864, and 0.832, respectively. The diagnostic efficiency of the four indicators were of similar (P value > 0.05). A diagnostic model of compensated stage hepatitis B cirrhosis (GAPA) using logistic regression analysis was established: LogitP = 1/ [1 + exp (1.614-0.054 × GP73-0.045 × Age + 0.030 × PLT-0.015 × ALP)]. The AUC of the model was as high as 0.940 and the optimal cut-off value were 0.41. The corresponding diagnostic sensitivity and specificity were 0.92 and 0.82, respectively. The diagnostic efficiency was better than that of APRI, FIB-4, LSM and GP73 alone (P < 0.05). The AUC of GAPA was 0.877 in the pathological diagnosis group, which was similar to the diagnostic efficacy of LSM (0.891) and FIB-4 (0.847) (P > 0.1), but still superior to that of APRI (0.811) and GP73 alone (0.780) (P < 0.001).@*Conclusion@#GAPA, a diagnostic model for compensated stage hepatitis B cirrhosis established in this study, has a good diagnostic efficacy in both the clinical and pathological diagnosis group, and has certain auxiliary diagnostic value in the areas where resources are relatively scarce or where LSM has not been developed.

Effect and mechanism of microRNA-128 on proliferation and apoptosis of hepatocelluar carcinoma cells / 中华肝胆外科杂志

Objective To investigate the effect of microRNA-128 (miR-128) on the proliferation,apoptosis on the hepatoma cells.Methods The target genes of miR-128 were analyzed by using bioinformatics and dual luciferase reporter assay system.We overexpressed miR-128 in the MHCC97H cells and also infected the GP73 gene with virus in the cell.Cell proliferation was detected by cell counting kit and apoptosis was detected by TUNEL and apoptosis index was calculated.Thirty 6-8 weeks Balb/c nude mice were randomly divided into miR-128 overexpression group (n =15) and control group (n =15).Results The results of bioinformatics and dual luciferase reporter assay showed that GP73 was the target gene of miR-128.Compared with the negative control group,cell proliferation in miR-128 overexpression group was decreased significantly;compared with miR-128 + empty plasmid group,cell in miR-128 + GP73 group was significantly increased (P ＜ 0.05).Compared with the negative control group,the apoptosis index in miR-128 overexpression group was significantly increased (P ＜ 0.05).Compared with miR-128 + empty plasmid group,the apoptosis index of miR-128 + GP73 group was significantly increased (P ＜ 0.05).Tumor volume of the overexpression group was higher than that of the control group.5 weeks later,tumor volume of the miR-128 overexpression group (1 209 ± 108) mm3 was significantly higher than that of the control group (1 985 ± 298)mm3,the difference was statistically significant (P ＜ 0.05).Conclusion miR-128 can promote the proliferation and inhibit the apoptosis of bepatoma cells by regulating GP73,which provide a reference for the prognosis evaluation of hepatoma.

A novel oncolytic adenovirus inhibits hepatocellular carcinoma growth / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

OBJECTIVE@#To evaluate the inhibitory role of a novel oncolytic adenovirus (OA), GP73-SphK1sR-Ad5, on the growth of hepatocellular carcinoma (HCC).@*METHODS@#GP73-SphK1sR-Ad5 was constructed by integrating Golgi protein 73 (GP73) promoter and sphingosine kinase 1 (SphK1)-short hairpin RNA (shRNA) into adenovirus serotype 5 (Ad5), and transfecting into HCC Huh7 cells and normal human liver HL-7702 cells. The expression of SphK1 and adenovirus early region 1 (E1A) was detected by quantitative real-time PCR (qRT-PCR) and western blot, respectively. Cell viability was detected by methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay, and apoptotic rate was determined by flow cytometry. An Huh7 xenograft model was established in mice injected intratumorally with GP73-SphK1sR-Ad5. Twenty days after injection, the tumor volume and weight, and the survival time of the mice were recorded. The histopathological changes in tumor tissues were observed by hematoxylin-eosin (HE) staining and transmission electron microscopy (TEM).@*RESULTS@#Transfection of GP73-SphK1sR-Ad5 significantly upregulated E1A and downregulated SphK1 in Huh7 cells, but not in HL7702 cells. GP73-SphK1sR-Ad5 transfection significantly decreased the viability and increased the apoptotic rate of Huh7 cells, but had no effect on HL7702 cells. Intratumoral injection of GP73-SphK1sR-Ad5 into the Huh7 xenograft mouse model significantly decreased tumor volume and weight, and prolonged survival time. It also significantly decreased the tumor infiltration area and blood vessel density, and increased the percentages of cells with nucleus deformation and cells with condensed chromatin in tumor tissues.@*CONCLUSIONS@#GP73-SphK1sR-Ad5 serves as a novel OA and can inhibit HCC progression with high specificity and efficacy.

The biological characteristics of GP73 and its value in the diagnosis of liver fibrosis and cirrhosis / 临床肝胆病杂志

Liver fibrosis is a necessary stage in the development of chronic liver diseases to liver cirrhosis. Liver cirrhosis is the end-stage change of various chronic liver diseases, and early diagnosis of liver fibrosis has an important value in timely treatment and prognosis. At present, liver biopsy, ultrasound, computed tomography, and magnetic resonance imaging are the main diagnostic methods for liver fibrosis and cirrhosis. Liver biopsy is the gold standard for the diagnosis of liver fibrosis and cirrhosis, but its clinical application is limited by invasiveness and sample error. Conventional noninvasive methods cannot meet the requirements for the diagnosis of liver fibrosis and cirrhosis. Therefore, searching for new serological markers for liver fibrosis and cirrhosis has become a research hotspot. Related studies have shown that serum Golgi protein 73 (GP73) can be used as a serum marker for the diagnosis of liver fibrosis and cirrhosis and has high clinical value. This article reviews the commonly used methods for the diagnosis of liver fibrosis and cirrhosis and elaborates on the biological characteristics of GP73 and its value in the diagnosis of liver fibrosis and cirrhosis.

The relationship between serum Golgi protein 73 and both liver inflammation and fibrosis in patients with chronic hepatitis B / 解放军医学杂志

Objective To explore the correlation between serum Golgi protein 73(GP73) and both liver inflammation and fibrosis in patients with chronic hepatitis B(CHB). Methods Altogether 322 patients who underwent liver biopsy were enrolled in this retrospective study, and GP73, ALT, AST, LSM, FIB-4, APRI were analyzed. The relationship between serum GP73 and both liver inflammation and fibrosis was analyzed. Univariate and multivariate logistic regression analysis were used to evaluate the predictive value of GP73 for significant liver injury. Results 322 CHB patients ranged from 18 to 66 years old, including 231 males (71.7%) and 91 females (28.3%), and the median of GP73 was 65.6(35.8-129.6) ng/ml. The serum level of GP73 stepwise increased with increase of liver inflammation grade and liver fibrosis stage, and GP73 was significantly correlated with liver inflammation grade (?=0.536, P<0.001) and fibrosis stage (?=0.536, P<0.001). The degree of liver inflammation or fibrosis at the same stage was analyzed and the results indicated that the serum GP73 levels were significantly correlated with the severity of liver inflammation, while the association between serum GP73 and the stage of liver fibrosis was weaker. In term of the advanced liver inflammation or fibrosis stage, univariate and multivariate analysis revealed that GP73 was simultaneously determined as an independent risk factor for predicting liver inflammation (P<0.001) and fibrosis (P<0.05). Conclusion Serum GP73 is well correlated with liver inflammation and fibrosis in CHB patients, and it might be a new biomarker to predict liver inflammation and fibrosis.

A novel oncolytic adenovirus inhibits hepatocellular carcinoma growth / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Objective: To evaluate the inhibitory role of a novel oncolytic adenovirus (OA), GP73-SphK1sR-Ad5, on the growth of hepatocellular carcinoma (HCC). Methods: GP73-SphK1sR-Ad5 was constructed by integrating Golgi protein 73 (GP73) promoter and sphingosine kinase 1 (SphK1)-short hairpin RNA (shRNA) into adenovirus serotype 5 (Ad5), and transfecting into HCC Huh7 cells and normal human liver HL-7702 cells. The expression of SphK1 and adenovirus early region 1 (E1A) was detected by quantitative real-time PCR (qRT-PCR) and western blot, respectively. Cell viability was detected by methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay, and apoptotic rate was determined by flow cytometry. An Huh7 xenograft model was established in mice injected intratumorally with GP73-SphK1sR-Ad5. Twenty days after injection, the tumor volume and weight, and the survival time of the mice were recorded. The histopathological changes in tumor tissues were observed by hematoxylin-eosin (HE) staining and transmission electron microscopy (TEM). Results: Transfection of GP73-SphK1sR-Ad5 significantly upregulated E1A and downregulated SphK1 in Huh7 cells, but not in HL7702 cells. GP73-SphK1sR-Ad5 transfection significantly decreased the viability and increased the apoptotic rate of Huh7 cells, but had no effect on HL7702 cells. Intratumoral injection of GP73-SphK1sR-Ad5 into the Huh7 xenograft mouse model significantly decreased tumor volume and weight, and prolonged survival time. It also significantly decreased the tumor infiltration area and blood vessel density, and increased the percentages of cells with nucleus deformation and cells with condensed chromatin in tumor tissues. Conclusions: GP73-SphK1sR-Ad5 serves as a novel OA and can inhibit HCC progression with high specificity and efficacy.

Development of a quantitative serum assay of Golgi protein 73 in hepatocellular carcinoma using xMAP technology / 中华肿瘤杂志

Objective@#To establish a quantitative assay of serum Golgi protein 73 (GP73) using xMAP technology and evaluate its performance.@*Methods@#Monoclonal antibodies against GP73 were prepared and purified, and antibody pair screening was performed by double-antibody sandwich enzyme-linked immunosorbent assay. The screened antibodies were used to construct a Luminex liquid chip detection system, and the analysis performance of the detection system was evaluated. The serum levels of GP73 were detected in 90 clinical samples from healthy controls and patients with chronic hepatitis B infection (CHB) and hepatocellular carcinoma (HCC).@*Results@#Five anti-GP73 monoclonal antibodies were prepared and purified, and 5 antibody pairs were successfully screened. The Luminex liquid chip detection system of GP73 was successfully constructed using 8F10D1 and 10B9F11 antibody pairs. The analytical performance evaluation showed that the sensitivity of this system was 0.25 ng/ml and the dynamic range was 0.25-100 ng/ml. No cross reactivity was observed. The intra- and inter-assay variation for GP73 was <8% and <11%, respectively. The recovery was 83%-92%. The linear regression equation was y=1.141x+ 6.436 (r2=0.998 4, P<0.001). The GP73 concentrations in the serum samples of healthy control, CHB group, and HCC group were 42.8 (38.68, 55.90) ng/ml, 61.49 (43.59, 81) ng/ml, and 122.78 (49.36 liter, 264.55) ng/ml, respectively. The levels of GP73 in HCC group were significantly higher than those in CHB group and healthy controls (P<0.05). Moreover, the levels of GP73 in CHB group were significantly higher than those in healthy controls (P<0.05).@*Conclusions@#A liquid chip detection system of GP73 was successfully constructed. It provides a powerful tool for the clinical application of GP73 in the future.

Diagnostic application of serum GP73 and the relevant mechanism in the diagnosis of liver cirrhosis / 中华肝脏病杂志

Liver cirrhosis is the end-stage change of chronic liver diseases with various causative factors. The accurate diagnosis of liver cirrhosis in an early stage is very important for the timely treatment and prognosis of patients. A liver biopsy test is the gold standard for the diagnosis of liver cirrhosis; but its use is limited in clinical practices due to its invasive nature. The conventional non-invasive measures (APRI, FIB-4 and LSM) for diagnosis of liver cirrhosis could not fulfill the needs. Therefore, finding a new serological marker of liver cirrhosis has become a research hotspot. Based on literature review and our own results, we suggest that serum GP73 as the most potential serum marker for liver cirrhosis diagnosis. This review briefly introduces the application of serum GP73 in the diagnosis of liver cirrhosis and the potential mechanism relevant to its involvement in the development of liver cirrhosis.

Depletion of GP73 inhibits invasion and metastasis of hepatocellular carcinoma cells / 中华肿瘤杂志

Objective@#To explore the in vitro and in vivo effect of GP73 on the proliferation, invasion and metastasis in hepatocellular carcinoma.@*Methods@#GP73 gene was knocked out using CRISPR/Cas9 gene editing system in H22 and HepG2 cells, and stable knock out strains were constructed. The knockout efficiency was measured by western blot. Colony formation assay was used to detect the effect of GP73 on long-term survival ability. Cells were then highly synchronized in G1 phase upon treatment with cell synchronization reagents (mimosine), and the percentage of cells in G2/M phase at different time points was detected by flow cytometry. The invasive and metastasis abilities of hepatocellular carcinoma cells were detected by Transwell™ assay. Furthermore, the tumor formation abilities in vivo were examined using subcutaneous xenograft models.@*Results@#The stable knock out strains of GP73 in H22 and HepG2 cells were successfully established via puromycin selection. The number of colonies of GP73 knock out groups in HepG2 and H22 cells 10 days after transfection were 400±70 and 248±60, respectively. They were significantly lower than those in the control groups (980±40 and 1 100±50, respectively; P<0.01). In addition, GP73 knockout slowed down the cell cycle progression. Moreover, the cell numbers that had migrated to the underside of the filters were 312±50 and 305±49 in the GP73 knockout groups of HepG2 and H22 cells, respectively, significantly lower than 1 540±87 and 1 270±86 in the controls (P<0.01). For transwell invasion assay, the cell number that had invaded into the underside of the filters were 230±47 and 238±54 in the GP73 knockout groups of HepG2 and H22 cells, respectively, significantly lower than 648±74 and 596±63 in the controls(P<0.01). Furthermore, the tumor volume of GP73 knockout group was (70±170) mm3, significantly smaller than (1 200±110)mm3 of the control guoup (P<0.01).@*Conclusions@#GP73 knockout decreases the proliferation, invasive and migratory abilities of HepG2 and H22 cells in vitro and in vivo. GP73 may contribute to tumorigenesis of hepatocellular carcinoma.

Difference and clinical significance of serum GP73 between alcoholic liver disease and non-alcohol fatty liver disease / 中华实验和临床病毒学杂志

Objective@#The present study was designed to evaluate the clinical significance of serum GP73 in patients with alcohol liver disease.@*Methods@#Thirty-two patients with alcoholic liver disease (ALD), 40 patients with non-alcohol fatty liver disease(NFLAD), and 40 apparently healthy individuals were included in this study.@*Results@#Compared with Those of healthy control population(43.91±19.02 ng/ml), the serum GP73 levels in ALD patients(93.39±66.91 ng/ml) were significantly increased, and also markedly higher than those of NFLAD patients (55.38±21.00 ng/ml). Taken the NFALD as"healthy controls" population, and ALD population as"patients" , the GP73 may be used to differentiate the ALD from NFLAD. The area of ROC analysis was 0.66(95%CI: 0.52~0.80, P=0.02). We set 75.65 ng/ml as the cut-off value for ALD diagnosis, the sensitivity and specificity were 50.0% and 85.0% respectively.@*Conclusion@#Serum GP73 levels in ALD patients were significantly higher than those of NFALD patients. GP73 may be a new marker for differentiating ALD from NFALD.

Diagnostic Value of Serum GP73 Combined with Dickkopf-1 and AFP in Hepatocellular Carcinoma / 现代生物医学进展

Objective:To investigate the diagnostic value of serum GP73 combined with Dickkopf-1 and AFP in hepatocellular carcinoma.Methods:117 cases of hepatocellular carcinoma in our hospital were collected as hepatocellular carcinoma group,80 patients with hepatitis B virus as the hepatitis group,and randomly selected 80 healthy subjects as the control group from September 2014 to September 2016.The serums GP73,Dickkopf-1,AFP level of every group were detected by the enzyme-linked immunosorbent assay (ELISA),and the relationship between the GP73,Dickkopf-1,AFP between clinicopathological features were analyzed,the diagnostic value of GP73,Dickkopf-1 and AFP in hepatocellular carcinoma were analyzed.Results:The serums GP73,Dickkopf-1,AFP level of hepatocellular carcinoma group were higher than those of hepatitis group,control group,and the serum AFP level of hepatitis group was higher than that of control group,the difference was statistically significant (P＜0.05).The GP73,Dickkopf-1,AFP in patients with classification B～C were higher than those in classification A among the Child Pugh classification,the difference was statistically significant (P＜0.05).No statistical significance on difference of GP73,Dickkopf-1,AFP between different differentiation,tumor size,number of tumors was found (P＞0.05).The sensitivity,specificity,positice predictive value,negative predictive value,and accuracy of GP73+Dickkopf-1+AFP in the diagnosis of hepatocellular carcinoma were higher than those of GP73,Dickkopf-1,AFP respectively,the difference was statistically significant (P＜0.05).Conclusion:Serums GP73,Dickkopf-1,AFP in patients with hepatocellular carcinoma have high expression levels,combined with the three indicators can obviously improve the diagnostic value of hepatocellular carcinoma,which has clinically important reference value.

Expression and clinical significance of serum Golgi protein 73 in infantile hepatitis syndrome / 中华实用儿科临床杂志

Objective To investigate the expression and the possible clinical significance of serum Golgi protein(GP73)in infantile hepatitis syndrome(IHS)by different causes.Methods Totally 79 patients with IHS in Guangzhou Women and Children's Medical Center from February 2012 to December 2012 were enrolled in this study,including 15 cases with biliary atresia(BA)group,29 cases with infection(infection group),5 cases with neonatal intrahepatic cholestasis caused by citrin deficiency(NICCD group),and 30 cases with unknown etiology(idiopathic infantile hepatitis group).At the same time,30 healthy infants were enrolled as healthy control group.The serum levels of GP73 were determined by quantitative enzyme-linked immunosorbent assay(ELISA),and the children's liver function[alanine aminotransferase(ALT),aspartate aminotransferase(AST),total bilirubin(TBIL),direct bilirubin(DBIL),alkaline phosphatase(ALP),γ-glutamyl trans-peptidase(γ-GT),total bile acid(TBA)and albumin(ALB)] were measured by turbidimetric inhibition immuno assay.Then,the corresponding data were statistically analyzed.Results Serum GP73 in BA group,infection group,NICCD group,idiopathic infantile hepatitis group and the healthy control group were(296.6±67.5)μg/L,(185.1±66.4)μg/L,(199.2±87.1)μg/L,(181.7±74.2)μg/L and(65.3±17.0)μg/L,respectively.Serum γ-GT levels in BA group,infection group,NICCD group,idiopathic infantile hepatitis group and healthy control group were(764.7±775.8)U/L,(448.2±352.7)U/L,(239.4±88.7)U/L,(283.3±377.2)U/L and(54.0±72.6)U/L,respectively.The levels of GP73 and γ-GT were significantly higher in infants with IHS,and the levels of GP73 and γ-GT in infants with BA were the highest(F=46.775,9.238,all P0.05).The receiver operating characteristic curve(ROC)constructed with GP73 showed a sensitivity of 80.0％and specificity of 82.8％with an area under the receiver(AUC)of 0.872 for diagnosis of BA,comparatively,a sensitivity of 66.7％and specificity of 71.9％were showed with a AUC of 0.731 when performed with γ-GT.Conclusions Serum GP73 concentration significantly increased in all liver disease groups,regardless of the etiology.Serum GP73 expression is significantly higher in infants with BA.Serum GP73 shows a superior sensitivity and specificity to γ-GT for diagnosis of BA,which might be useful for early diagnosis of BA and IHS with different causes.

Serological diagnosis of hepatocellular carcinoma: challenges and opportunities / 临床肝胆病杂志

Serological markers have the features of noninvasiveness and simple operation and thus have become a research hotspot in the diagnosis of hepatocellular carcinoma.This article briefly introduces the role of the conventional serological marker alpha-fetoprotein (AFP) in assisting the diagnosis and predicting the prognosis of HBV-related liver cancer, as well as the clinical value of new markers such as alpha-fetoprotein-L3 and abnormal prothrombin/des-γ-carboxy prothrombin.Based on literature review, the possibility of serum Golgi protein 73 used for laboratory auxiliary diagnosis of hepatocellular carcinoma has been denied.The results of the author′s experiment suggest that serum GP73 measurement can be used as a laboratory diagnostic index for progressive liver fibrosis and liver cirrhosis.

Forewarning value of AFP and GP7 3 detection in canceration of patients with liver cirrhosis / 国际检验医学杂志

Objective To evaluate the forewarning value of alpha-fetoprotein (AFP)and golgi protein73(GP73)in canceration of the patients with liver cirrhosis.Methods The levels of AFP and GP73 were respectively tested by chemiluminescence immuno-assay and ELISA.Fifty patients with liver cirrhosis were performed 24-month follow up for understanding the liver cancer occur-rence situation.The value of AFP and GP73 for predicting the liver cancer occurrence risk in the patients with liver cirrhosis was analyzed and compared.Results The canceration rate after 18,24 months follow up in the liver cirrhosis patients with GPP(+) was significantly higher than that with AFP(+),the difference was statistically significant(P>0.05).Conclusion AFP and GP-73 all have the predictive value for canceration of liver cirrhosis,moreover GP73 has more forewarning value.