BACKGROUND Reliable biomarkers of cirrhosis,hepatocellular carcinoma(HCC),or progression of chronic liver diseases are missing.In this context,Golgi protein-73(GP73)also called Golgi phosphoprotein-2,was originally de...BACKGROUND Reliable biomarkers of cirrhosis,hepatocellular carcinoma(HCC),or progression of chronic liver diseases are missing.In this context,Golgi protein-73(GP73)also called Golgi phosphoprotein-2,was originally defined as a resident Golgi type II transmembrane protein expressed in epithelial cells.As a result,GP73 expression was found primarily in biliary epithelial cells,with only slight detection in hepatocytes.However,in patients with acute or chronic liver diseases and especially in HCC,the expression of GP73 is significantly up-regulated in hepatocytes.So far,few studies have assessed GP73 as a diagnostic or prognostic marker of liver fibrosis and disease progression.AIM To assess serum GP73 efficacy as a diagnostic marker of cirrhosis and/or HCC or as predictor of liver disease progression.METHODS GP73 serum levels were retrospectively determined by a novel GP73 ELISA(QUANTA Lite®GP73,Inova Diagnostics,Inc.,Research Use Only)in a large cohort of 632 consecutive patients with chronic viral and non-viral liver diseases collected from two tertiary Academic centers in Larissa,Greece(n=366)and Debrecen,Hungary(n=266).Aspartate aminotransferase(AST)/Platelets(PLT)ratio index(APRI)was also calculated at the relevant time points in all patients.Two hundred and three patients had chronic hepatitis B,183 chronic hepatitis C,198 alcoholic liver disease,28 autoimmune cholestatic liver diseases,15 autoimmune hepatitis,and 5 with other liver-related disorders.The duration of follow-up was 50(57)mo[median(interquartile range)].The development of cirrhosis,liver decompensation and/or HCC during follow-up were assessed according to internationally accepted guidelines.In particular,the surveillance for the development of HCC was performed regularly with ultrasound imaging and alpha-fetoprotein(AFP)determination every 6 mo in cirrhotic and every 12 mo in non-cirrhotic patients.RESULTS Increased serum levels of GP73(>20 units)were detected at initial evaluation in 277 out of 632 patients(43.8%).GP73-seropositivity correlated at baseline with the presence of cirrhosis(96.4%vs 51.5%,P<0.001),decompensation of cirrhosis(60.3%vs 35.5%,P<0.001),presence of HCC(18.4%vs 7.9%,P<0.001)and advanced HCC stage(52.9%vs 14.8%,P=0.002).GP73 had higher diagnostic accuracy for the presence of cirrhosis compared to APRI score[Area under the curve(AUC)(95%CI):0.909(0.885-0.934)vs 0.849(0.813-0.886),P=0.003].Combination of GP73 with APRI improved further the accuracy(AUC:0.925)compared to GP73(AUC:0.909,P=0.005)or APRI alone(AUC:0.849,P<0.001).GP73 levels were significantly higher in HCC patients compared to non-HCC[22.5(29.2)vs 16(20.3)units,P<0.001)and positively associated with BCLC stage[stage 0:13.9(10.8);stage A:17.1(16.8);stage B:19.6(22.3);stage C:32.2(30.8);stage D:45.3(86.6)units,P<0.001]and tumor dimensions[very early:13.9(10.8);intermediate:19.6(18.4);advanced:29.1(33.6)units,P=0.004].However,the discriminative ability for HCC diagnosis was relatively low[AUC(95%CI):0.623(0.570-0.675)].Kaplan-Meier analysis showed that the detection of GP73 in patients with compensated cirrhosis at baseline,was prognostic of higher rates of decompensation(P=0.036),HCC development(P=0.08),and liver-related deaths(P<0.001)during follow-up.CONCLUSION GP73 alone appears efficient for detecting cirrhosis and superior to APRI determination.In combination with APRI,its diagnostic performance can be further improved.Most importantly,the simple GP73 measurement proved promising for predicting a worse outcome of patients with both viral and nonviral chronic liver diseases.展开更多
目的基于GALAD模型分析高尔基体糖蛋白-73(Golgi protein 73,GP73)和肝脏硬度测量值(liver stiffness measurement,LSM)在丙型肝炎病毒(hepatitis C virus,HCV)相关肝细胞癌(hepatocellular carcinoma,HCC)患者中表达及诊断价值。方法选...目的基于GALAD模型分析高尔基体糖蛋白-73(Golgi protein 73,GP73)和肝脏硬度测量值(liver stiffness measurement,LSM)在丙型肝炎病毒(hepatitis C virus,HCV)相关肝细胞癌(hepatocellular carcinoma,HCC)患者中表达及诊断价值。方法选取2019年1月至2022年1月西安交通大学第一附属医院榆林医院收治的75例慢性HCV感染并确诊HCC患者(HCC组)和85例HCV感染非HCC患者(对照组)作为研究对象。采用全自动生化仪检测两组患者肝功能生化指标;采用全自动化学发光免疫分析仪分析两组患者甲胎蛋白(α-fetoprotein,AFP)、甲胎蛋白异构体L3(α-fetoprotein-L3,AFP-L3)、异常凝血酶原(des-γ-carboxy prothrombin,DCP)及GP73水平,并根据公式计算GALAD模型得分;采用肝纤维化无创扫描仪测量LSM;采用受试者工作特征曲线分析HCC诊断价值;采用Pearson相关方法进行相关性分析。结果HCC组患者肝功能指标、AFP、DCP、AFP-L3、LSM、GP73水平及GALAD模型评分均显著高于对照组(均P<0.05);HCC组患者不同肿瘤分期亚组AFP、DCP、AFP-L3、LSM、GP73水平及GALAD模型评分比较差异均有统计学意义(均P<0.05),且分期越晚指标水平和GALAD模型评分越高,各分期亚组间差异均有统计学意义(均P<0.05)。相关性分析显示,LSM、GP73水平与GALAD模型评分均呈线性正相关(r=0.622,P<0.001;r=0.532,P<0.001)。LSM、GP73及GALAD三项联合诊断HCC的曲线下面积为0.933,检测敏感度为94.56%,特异度为83.23%,均显著高于单独诊断(均P<0.05)。结论GALAD模型在HCV相关HCC诊断中显示了良好的效能,LSM、GP73作为HCC诊断标志物与GALAD模型评分呈正相关,且联合GALAD模型对HCC表现出更好的诊断效能。展开更多
目的:分析高尔基体蛋白73(Golgi protein 73,GP73)、甲胎蛋白(Alpha-fetoprotein,AFP)及肝功能指标与原发性肝癌(以下简称“肝癌”)中医证型之间的相关性。方法:选取156例肝癌患者(肝癌组)、52例健康体检者(健康组)为研究对象,检测其GP7...目的:分析高尔基体蛋白73(Golgi protein 73,GP73)、甲胎蛋白(Alpha-fetoprotein,AFP)及肝功能指标与原发性肝癌(以下简称“肝癌”)中医证型之间的相关性。方法:选取156例肝癌患者(肝癌组)、52例健康体检者(健康组)为研究对象,检测其GP73、AFP表达及肝功能相关指标水平,对所得数据资料采用SPSS21.0软件进行统计分析。结果:(1)肝癌组GP73阳性表达率为50%;气滞血瘀证、肝胆热毒证、肝肾阴虚证阳性表达率分别为37.9%、54.3%、59.6%,组间比较,差异无统计学意义(P>0.05)。AFP阳性表达率为41.7%;气滞血瘀证、肝胆热毒证、肝肾阴虚证阳性表达率分别为32.8,41.3和51.9%,组间比较,差异有统计学意义(P<0.05)。(2)肝癌组不同证型患者GP73水平从高到低依次为肝肾阴虚证、肝胆热毒证、气滞血瘀证,组间比较,差异有统计学意义(P<0.05)。肝癌组不同证型患者AFP水平从高到低依次为肝胆热毒证、肝肾阴虚证、气滞血瘀证,组间比较,差异无统计学意义(P>0.05)。(3)肝癌组肝功能指标分析:不同证型患者ALT水平从高到低依次为肝肾阴虚证、肝胆热毒证、气滞血瘀证,组间比较,差异有统计学意义(P<0.05);不同证型患者AST水平从高到低依次为肝胆热毒证、肝肾阴虚证、气滞血瘀证,组间比较,差异有统计学意义(P<0.05);不同证型患者ALB水平从高到低依次为肝胆热毒证、气滞血瘀证、肝肾阴虚证,组间比较,差异有统计学意义(P<0.05)。结论:GP73及ALT、AST、ALB等指标对肝癌患者中医辨证分型的诊断具有重要意义。展开更多
BACKGROUND： Golgi protein 73 （GP73） is a promising bio- marker of hepatocellular carcinoma （HCC）. It decreases after surgical resection, and resumes upon recurrence, indicating a potential indicator for the effec...BACKGROUND： Golgi protein 73 （GP73） is a promising bio- marker of hepatocellular carcinoma （HCC）. It decreases after surgical resection, and resumes upon recurrence, indicating a potential indicator for the effectiveness of the treatment. But changes of GP73 after transcatheter arterial chemoemboliza- tion （TACE） have not been reported so far. This study was to investigate the dynamic changes of GP73 in HCC patients af- ter TACE treatment, and the possible underlying mechanisms in the cell cultures. METHODS： Blood samples were collected from 72 HCC pa- tients, before TACE, at day I and day 30 after TACE. GP73 lev- els were measured by Western blotting. The dynamic changes of GP73 were analyzed and compared with image changes and clinical data. The effects of chemotherapeutic agents （5-FU and pirarubicin） on GP73 expression were tested in three HCC cell lines （HepG2, HCCLM3 and MHCC97H）. RESULTS： The GP73 level was significantly elevated at day 1 and day 30 after TACE in HCC patients compared with that before the procedure （P〈0.05）. There was no statistical differ- ence between the two time points after TACE, nor correlationbetween GP73 levels and dinicopathological features, tumor metastasis, and patient survival. Pirarubicin, not 5-FU, signifi- cantly increased GP73 expression in three cell lines. CONCLUSIONS： Unlike surgical resection which decreases the GP73 level, TACE significantly increased GP73 expression in patients with HCC. No correlations were observed among GP73 levels, tumor characteristics and prognosis of patients with HCC.展开更多
文摘BACKGROUND Reliable biomarkers of cirrhosis,hepatocellular carcinoma(HCC),or progression of chronic liver diseases are missing.In this context,Golgi protein-73(GP73)also called Golgi phosphoprotein-2,was originally defined as a resident Golgi type II transmembrane protein expressed in epithelial cells.As a result,GP73 expression was found primarily in biliary epithelial cells,with only slight detection in hepatocytes.However,in patients with acute or chronic liver diseases and especially in HCC,the expression of GP73 is significantly up-regulated in hepatocytes.So far,few studies have assessed GP73 as a diagnostic or prognostic marker of liver fibrosis and disease progression.AIM To assess serum GP73 efficacy as a diagnostic marker of cirrhosis and/or HCC or as predictor of liver disease progression.METHODS GP73 serum levels were retrospectively determined by a novel GP73 ELISA(QUANTA Lite®GP73,Inova Diagnostics,Inc.,Research Use Only)in a large cohort of 632 consecutive patients with chronic viral and non-viral liver diseases collected from two tertiary Academic centers in Larissa,Greece(n=366)and Debrecen,Hungary(n=266).Aspartate aminotransferase(AST)/Platelets(PLT)ratio index(APRI)was also calculated at the relevant time points in all patients.Two hundred and three patients had chronic hepatitis B,183 chronic hepatitis C,198 alcoholic liver disease,28 autoimmune cholestatic liver diseases,15 autoimmune hepatitis,and 5 with other liver-related disorders.The duration of follow-up was 50(57)mo[median(interquartile range)].The development of cirrhosis,liver decompensation and/or HCC during follow-up were assessed according to internationally accepted guidelines.In particular,the surveillance for the development of HCC was performed regularly with ultrasound imaging and alpha-fetoprotein(AFP)determination every 6 mo in cirrhotic and every 12 mo in non-cirrhotic patients.RESULTS Increased serum levels of GP73(>20 units)were detected at initial evaluation in 277 out of 632 patients(43.8%).GP73-seropositivity correlated at baseline with the presence of cirrhosis(96.4%vs 51.5%,P<0.001),decompensation of cirrhosis(60.3%vs 35.5%,P<0.001),presence of HCC(18.4%vs 7.9%,P<0.001)and advanced HCC stage(52.9%vs 14.8%,P=0.002).GP73 had higher diagnostic accuracy for the presence of cirrhosis compared to APRI score[Area under the curve(AUC)(95%CI):0.909(0.885-0.934)vs 0.849(0.813-0.886),P=0.003].Combination of GP73 with APRI improved further the accuracy(AUC:0.925)compared to GP73(AUC:0.909,P=0.005)or APRI alone(AUC:0.849,P<0.001).GP73 levels were significantly higher in HCC patients compared to non-HCC[22.5(29.2)vs 16(20.3)units,P<0.001)and positively associated with BCLC stage[stage 0:13.9(10.8);stage A:17.1(16.8);stage B:19.6(22.3);stage C:32.2(30.8);stage D:45.3(86.6)units,P<0.001]and tumor dimensions[very early:13.9(10.8);intermediate:19.6(18.4);advanced:29.1(33.6)units,P=0.004].However,the discriminative ability for HCC diagnosis was relatively low[AUC(95%CI):0.623(0.570-0.675)].Kaplan-Meier analysis showed that the detection of GP73 in patients with compensated cirrhosis at baseline,was prognostic of higher rates of decompensation(P=0.036),HCC development(P=0.08),and liver-related deaths(P<0.001)during follow-up.CONCLUSION GP73 alone appears efficient for detecting cirrhosis and superior to APRI determination.In combination with APRI,its diagnostic performance can be further improved.Most importantly,the simple GP73 measurement proved promising for predicting a worse outcome of patients with both viral and nonviral chronic liver diseases.
文摘目的基于GALAD模型分析高尔基体糖蛋白-73(Golgi protein 73,GP73)和肝脏硬度测量值(liver stiffness measurement,LSM)在丙型肝炎病毒(hepatitis C virus,HCV)相关肝细胞癌(hepatocellular carcinoma,HCC)患者中表达及诊断价值。方法选取2019年1月至2022年1月西安交通大学第一附属医院榆林医院收治的75例慢性HCV感染并确诊HCC患者(HCC组)和85例HCV感染非HCC患者(对照组)作为研究对象。采用全自动生化仪检测两组患者肝功能生化指标;采用全自动化学发光免疫分析仪分析两组患者甲胎蛋白(α-fetoprotein,AFP)、甲胎蛋白异构体L3(α-fetoprotein-L3,AFP-L3)、异常凝血酶原(des-γ-carboxy prothrombin,DCP)及GP73水平,并根据公式计算GALAD模型得分;采用肝纤维化无创扫描仪测量LSM;采用受试者工作特征曲线分析HCC诊断价值;采用Pearson相关方法进行相关性分析。结果HCC组患者肝功能指标、AFP、DCP、AFP-L3、LSM、GP73水平及GALAD模型评分均显著高于对照组(均P<0.05);HCC组患者不同肿瘤分期亚组AFP、DCP、AFP-L3、LSM、GP73水平及GALAD模型评分比较差异均有统计学意义(均P<0.05),且分期越晚指标水平和GALAD模型评分越高,各分期亚组间差异均有统计学意义(均P<0.05)。相关性分析显示,LSM、GP73水平与GALAD模型评分均呈线性正相关(r=0.622,P<0.001;r=0.532,P<0.001)。LSM、GP73及GALAD三项联合诊断HCC的曲线下面积为0.933,检测敏感度为94.56%,特异度为83.23%,均显著高于单独诊断(均P<0.05)。结论GALAD模型在HCV相关HCC诊断中显示了良好的效能,LSM、GP73作为HCC诊断标志物与GALAD模型评分呈正相关,且联合GALAD模型对HCC表现出更好的诊断效能。
基金supported by the Tackling of Science and Technology Research Project in Henan Province(182102310319)Special Project for the Scientific Research of Traditional Chinese Medicine in Henan Province(2022ZY1167)National famous TCM Experts Inheritance Studio Construction Project(Education Letter from the Office of the State Administration of Traditional Chinese Medicine[2018]119).
文摘目的:分析高尔基体蛋白73(Golgi protein 73,GP73)、甲胎蛋白(Alpha-fetoprotein,AFP)及肝功能指标与原发性肝癌(以下简称“肝癌”)中医证型之间的相关性。方法:选取156例肝癌患者(肝癌组)、52例健康体检者(健康组)为研究对象,检测其GP73、AFP表达及肝功能相关指标水平,对所得数据资料采用SPSS21.0软件进行统计分析。结果:(1)肝癌组GP73阳性表达率为50%;气滞血瘀证、肝胆热毒证、肝肾阴虚证阳性表达率分别为37.9%、54.3%、59.6%,组间比较,差异无统计学意义(P>0.05)。AFP阳性表达率为41.7%;气滞血瘀证、肝胆热毒证、肝肾阴虚证阳性表达率分别为32.8,41.3和51.9%,组间比较,差异有统计学意义(P<0.05)。(2)肝癌组不同证型患者GP73水平从高到低依次为肝肾阴虚证、肝胆热毒证、气滞血瘀证,组间比较,差异有统计学意义(P<0.05)。肝癌组不同证型患者AFP水平从高到低依次为肝胆热毒证、肝肾阴虚证、气滞血瘀证,组间比较,差异无统计学意义(P>0.05)。(3)肝癌组肝功能指标分析:不同证型患者ALT水平从高到低依次为肝肾阴虚证、肝胆热毒证、气滞血瘀证,组间比较,差异有统计学意义(P<0.05);不同证型患者AST水平从高到低依次为肝胆热毒证、肝肾阴虚证、气滞血瘀证,组间比较,差异有统计学意义(P<0.05);不同证型患者ALB水平从高到低依次为肝胆热毒证、气滞血瘀证、肝肾阴虚证,组间比较,差异有统计学意义(P<0.05)。结论:GP73及ALT、AST、ALB等指标对肝癌患者中医辨证分型的诊断具有重要意义。
基金supported by grants from the National Key Technology Research and Development Program of China 2012(BAI06B01)the National Natural Science Foundation of China(81201566)+1 种基金the Specialized Research Fund for the Doctoral Program of Higher Education(20121106110002)Wu Jieping Medical Foundation(LDWMF-SY-2011B002)
文摘BACKGROUND： Golgi protein 73 （GP73） is a promising bio- marker of hepatocellular carcinoma （HCC）. It decreases after surgical resection, and resumes upon recurrence, indicating a potential indicator for the effectiveness of the treatment. But changes of GP73 after transcatheter arterial chemoemboliza- tion （TACE） have not been reported so far. This study was to investigate the dynamic changes of GP73 in HCC patients af- ter TACE treatment, and the possible underlying mechanisms in the cell cultures. METHODS： Blood samples were collected from 72 HCC pa- tients, before TACE, at day I and day 30 after TACE. GP73 lev- els were measured by Western blotting. The dynamic changes of GP73 were analyzed and compared with image changes and clinical data. The effects of chemotherapeutic agents （5-FU and pirarubicin） on GP73 expression were tested in three HCC cell lines （HepG2, HCCLM3 and MHCC97H）. RESULTS： The GP73 level was significantly elevated at day 1 and day 30 after TACE in HCC patients compared with that before the procedure （P〈0.05）. There was no statistical differ- ence between the two time points after TACE, nor correlationbetween GP73 levels and dinicopathological features, tumor metastasis, and patient survival. Pirarubicin, not 5-FU, signifi- cantly increased GP73 expression in three cell lines. CONCLUSIONS： Unlike surgical resection which decreases the GP73 level, TACE significantly increased GP73 expression in patients with HCC. No correlations were observed among GP73 levels, tumor characteristics and prognosis of patients with HCC.
