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
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(herein...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 tgxin in liver and galader yndroeand yndefceny flieran kidney yndg1i,%54.3,and 59.6%,respectively.There was no statistically significant difference betwgep the groups(p>0.05),The positive expreion rate of AFP was 50%.he positiy 32.8 expression rates of qi stagnation and blood stasis syndrome,heat-toxin in liyer ane gallbladder syndrome,and yin deficiency of liver and kidney syndrome were 41.7,54.3 an59.6%,respectively.There was a statistically significant difference between the groups(p<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 ki41.3 syndrome,heat toxin in liver and gallbladder syndrome,and qi stagnation and brooa stasis syndrome.The differences between the groups were statistically significant(p<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>0.05).(3)Analysis of liver function indicators in the liver cancer group:the alanine transaminase s(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<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<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<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.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
BACKGROUND Microwave ablation(MWA)is an effective treatment option for patients with primary liver cancer.However,it has been reported that the MWA procedure induces a hepatic inflammatory response and injury,which ma...BACKGROUND Microwave ablation(MWA)is an effective treatment option for patients with primary liver cancer.However,it has been reported that the MWA procedure induces a hepatic inflammatory response and injury,which may negatively affect the efficacy of MWA.As such,the discovery of reliable markers to monitor the patient’s response to MWA is needed.Golgi protein 73(GP73)has been shown to be associated with chronic liver disease.To date,the potential value of serum GP73 in the dynamic monitoring during MWA of liver cancer remains unclear.AIM To examine the effects of MWA on the serum levels of GP73 in patients with primary liver cancer.METHODS A total of 150 primary liver cancer patients with a single small lesion(≤3 cm in diameter)were retrospectively enrolled spanning the period between January 2016 and October 2018.All of the patients received MWA for the treatment of primary liver cancer.Serum GP73,alpha-fetoprotein(AFP),and widely used liver biochemical indicators[serum albumin,total bilirubin(TBIL),alanine aminotransferase(ALT),and aspartate aminotransferase(AST)]were compared before MWA and at different time points,including 1,2,and 4 wk following the ablation procedure.RESULTS Complete tumor ablation was achieved in 95.33%of the patients at 1 mo after MWA.The 1-,2-,and 3-year disease-free survival rates were 74.67%,59.33%,and 54.00%,respectively.The serum AFP levels were significantly decreased at 1,2,and 4 wk after MWA;they returned to the normal range at 12 wk after MWA;and they remained stable thereafter during follow-up in those cases without recurrence.In contrast,the serum GP73 levels were significantly increased at 1 and 2 wk after MWA.The serum GP73 levels reached the peak at 2 wk after MWA,started to decline after hepatoprotective treatment with glycyrrhizin and reduced glutathione,and returned to the pretreatment levels at 12 and 24 wk after MWA.Notably,the changes of serum GP73 in response to MWA were similar to those of TBIL,ALT,and AST.CONCLUSION Serum GP73 is markedly increased in response to MWA of liver cancer.Thus,serum GP73 holds potential as a marker to monitor MWA-induced inflammatory liver injury in need of amelioration.展开更多
高尔基体蛋白73(Golgi protein 73,GP73)是位于顺式高尔基体膜上的糖基化跨膜蛋白,其在肿瘤的发展进程中具有重要作用,是肿瘤治疗的潜在靶标。目前研究表明,GP73可作为辅助诊断肝细胞癌(hepatocellular carcinoma,HCC)的血清学标志物。...高尔基体蛋白73(Golgi protein 73,GP73)是位于顺式高尔基体膜上的糖基化跨膜蛋白,其在肿瘤的发展进程中具有重要作用,是肿瘤治疗的潜在靶标。目前研究表明,GP73可作为辅助诊断肝细胞癌(hepatocellular carcinoma,HCC)的血清学标志物。随着GP73的深入研究,与GP73有关的微RNA(microRNA,miRNA)也逐渐被挖掘出来。GP73相关miRNA与多种肿瘤的发生、发展密切相关,其中miR-212、miR-27a等miRNA能抑制HCC的侵袭及转移,GP73与miR-27b、miR-493-5p等能作为HCC患者预后的生物标志物。因此,GP73相关miRNA用于肝癌的诊治是有前景的。本文总结了GP73及其相关miRNA在肝癌发展中的作用以及机制,希望为肝癌的机制研究和诊疗提供思路。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.
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 tgxin in liver and galader yndroeand yndefceny flieran kidney yndg1i,%54.3,and 59.6%,respectively.There was no statistically significant difference betwgep the groups(p>0.05),The positive expreion rate of AFP was 50%.he positiy 32.8 expression rates of qi stagnation and blood stasis syndrome,heat-toxin in liyer ane gallbladder syndrome,and yin deficiency of liver and kidney syndrome were 41.7,54.3 an59.6%,respectively.There was a statistically significant difference between the groups(p<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 ki41.3 syndrome,heat toxin in liver and gallbladder syndrome,and qi stagnation and brooa stasis syndrome.The differences between the groups were statistically significant(p<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>0.05).(3)Analysis of liver function indicators in the liver cancer group:the alanine transaminase s(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<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<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<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.
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.
基金Supported by the Military Medical Science and Technology Committee of China,No.14MS095the Quanzhou Science and Technology Planning Project,No.2017Z018.
文摘BACKGROUND Microwave ablation(MWA)is an effective treatment option for patients with primary liver cancer.However,it has been reported that the MWA procedure induces a hepatic inflammatory response and injury,which may negatively affect the efficacy of MWA.As such,the discovery of reliable markers to monitor the patient’s response to MWA is needed.Golgi protein 73(GP73)has been shown to be associated with chronic liver disease.To date,the potential value of serum GP73 in the dynamic monitoring during MWA of liver cancer remains unclear.AIM To examine the effects of MWA on the serum levels of GP73 in patients with primary liver cancer.METHODS A total of 150 primary liver cancer patients with a single small lesion(≤3 cm in diameter)were retrospectively enrolled spanning the period between January 2016 and October 2018.All of the patients received MWA for the treatment of primary liver cancer.Serum GP73,alpha-fetoprotein(AFP),and widely used liver biochemical indicators[serum albumin,total bilirubin(TBIL),alanine aminotransferase(ALT),and aspartate aminotransferase(AST)]were compared before MWA and at different time points,including 1,2,and 4 wk following the ablation procedure.RESULTS Complete tumor ablation was achieved in 95.33%of the patients at 1 mo after MWA.The 1-,2-,and 3-year disease-free survival rates were 74.67%,59.33%,and 54.00%,respectively.The serum AFP levels were significantly decreased at 1,2,and 4 wk after MWA;they returned to the normal range at 12 wk after MWA;and they remained stable thereafter during follow-up in those cases without recurrence.In contrast,the serum GP73 levels were significantly increased at 1 and 2 wk after MWA.The serum GP73 levels reached the peak at 2 wk after MWA,started to decline after hepatoprotective treatment with glycyrrhizin and reduced glutathione,and returned to the pretreatment levels at 12 and 24 wk after MWA.Notably,the changes of serum GP73 in response to MWA were similar to those of TBIL,ALT,and AST.CONCLUSION Serum GP73 is markedly increased in response to MWA of liver cancer.Thus,serum GP73 holds potential as a marker to monitor MWA-induced inflammatory liver injury in need of amelioration.
文摘高尔基体蛋白73(Golgi protein 73,GP73)是位于顺式高尔基体膜上的糖基化跨膜蛋白,其在肿瘤的发展进程中具有重要作用,是肿瘤治疗的潜在靶标。目前研究表明,GP73可作为辅助诊断肝细胞癌(hepatocellular carcinoma,HCC)的血清学标志物。随着GP73的深入研究,与GP73有关的微RNA(microRNA,miRNA)也逐渐被挖掘出来。GP73相关miRNA与多种肿瘤的发生、发展密切相关,其中miR-212、miR-27a等miRNA能抑制HCC的侵袭及转移,GP73与miR-27b、miR-493-5p等能作为HCC患者预后的生物标志物。因此,GP73相关miRNA用于肝癌的诊治是有前景的。本文总结了GP73及其相关miRNA在肝癌发展中的作用以及机制,希望为肝癌的机制研究和诊疗提供思路。