Research progress of novel serum marker Golgi protein 73 in clinical diagnosis and treatment of chronic hepatitis B_West China Medical Journal

Authors：

ZHANG Huan ,  LEI Xuezhong

Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P. R. China;

Corresponding author：

LEI Xuezhong, Email: 18980601317@163.com

Keywords：

Golgi protein 73; chronic hepatitis B; clinical value; research progress

DOI：

10.7507/1002-0179.202303089

Video：

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Abstract Full text Figures/Tables Video References Cited by

Serum marker Golgi protein 73 (GP73) is a type Ⅱ integral membrane protein located in cellular Golgi apparatus. GP73 not only processes proteins, but also participates in cell differentiation, intercellular signaling, and apoptosis. With the development of proteomics technology, GP73 has been used as a novel serum marker for detecting liver diseases. This article reviews the research progress of GP73 in the clinical diagnosis value and prognosis prediction of chronic hepatitis B in recent years, in order to provide new ideas for the diagnosis and treatment of patients with chronic hepatitis B.

Citation： ZHANG Huan, LEI Xuezhong. Research progress of novel serum marker Golgi protein 73 in clinical diagnosis and treatment of chronic hepatitis B. West China Medical Journal, 2023, 38(8): 1243-1246. doi: 10.7507/1002-0179.202303089 Copy

1.	Kladney RD, Bulla GA, Guo L, et al. GP73, a novel Golgi-localized protein upregulated by viral infection. Gene, 2000, 249(1/2): 53-65.
2.	Rosa-Ferreira C, Christis C, Torres IL, et al. The small G protein Arl5 contributes to endosome-to-Golgi traffic by aiding the recruitment of the GARP complex to the Golgi. Biol Open, 2015, 4(4): 474-481.
3.	Cao Z, Li Z, Wang H, et al. Algorithm of Golgi protein 73 and liver stiffness accurately diagnoses significant fibrosis in chronic HBV infection. Liver Int, 2017, 37(11): 1612-1621.
4.	Block TM, Comunale MA, Lowman M, et al. Use of targeted glycoproteomics to identify serum glycoproteins that correlate with liver cancer in woodchucks and humans. Proc Natl Acad Sci U S A, 2005, 102(3): 779-784.
5.	Gatselis NK, Zachou K, Giannoulis G, et al. Serum cartilage oligomeric matrix protein and Golgi protein-73: new diagnostic and predictive tools for liver fibrosis and hepatocellular cancer?. Cancers (Basel), 2021, 13(14): 3510.
6.	Dong M, Chen ZH, Li X, et al. Serum Golgi protein 73 is a prognostic rather than diagnostic marker in hepatocellular carcinoma. Oncol Lett, 2017, 14(5): 6277-6284.
7.	Liang R, Liu Z, Piao X, et al. Research progress on GP73 in malignant tumors. Onco Targets Ther, 2018, 11: 7417-7421.
8.	田霞. 血清 GDF-15、GP73、AFP 对肝细胞癌的诊断价值研究. 检验医学与临床, 2021, 18(16): 2438-2440.
9.	潘俊均, 黄仙圣, 岑伟明, 等. AFP、AFP-L3%、DCP 与 GP73 联合检测辅助诊断肝炎、肝癌临床价值. 分子诊断与治疗杂志, 2021, 13(10): 1579-1582.
10.	林召, 党小军, 侯智辉, 等. 血清 FFA、GP73 水平变化与慢性乙型肝炎患者病情程度的关联性及临床意义探讨. 泰山医学院学报, 2018, 39(8): 921-923.
11.	贾芳岩, 佘亚辉, 余明杰, 等. 慢性乙型肝炎患者血清 AFP-L3、GP73、AFP 水平变化及临床价值研究. 国际检验医学杂志, 2020, 41(12): 1527-1529.
12.	郑志恒, 李维筠, 回振宇, 等. 聚乙二醇干扰素α-2a 联合恩替卡韦治疗慢性乙型肝炎患者疗效及血清 Pygo2 和 GP73 水平变化. 实用肝脏病杂志, 2021, 24(1): 19-22.
13.	Peng Y, Zeng Q, Wan L, et al. GP73 is a TBC-domain Rab GTPase-activating protein contributing to the pathogenesis of non-alcoholic fatty liver disease without obesity. Nat Commun, 2021, 12(1): 7004.
14.	Wang L, Yao M, Liu S, et al. Serum Golgi protein 73 as a potential biomarker for hepatic necroinflammation in population with nonalcoholic steatohepatitis. Dis Markers, 2020, 2020: 6036904.
15.	Xu Z, Shen J, Pan X, et al. Predictive value of serum Golgi protein 73 for prominent hepatic necroinflammation in chronic HBV infection. J Med Virol, 2018, 90(6): 1053-1062.
16.	张晓坤, 司徒瑞儒. 甲胎蛋白、甲胎蛋白异质体 3 比率、高尔基体蛋白 73 联合检测在原发性肝癌诊断中的价值. 实用医学杂志, 2021, 37(8): 1068-1071.
17.	袁吉磊, 黄辉, 成强. 血清前白蛋白联合高尔基体蛋白 73 在肝病检测及治疗过程中的应用. 中国社区医师, 2017, 33(3): 108-109.
18.	向琴. 血清 GP73 在 HBV 感染的慢性重型肝炎患者的表达水平及其对短期预后的预测价值. 南充: 川北医学院, 2018.
19.	Yao M, Wang L, You H, et al. Serum GP73 combined AST and GGT reflects moderate to severe liver inflammation in chronic hepatitis B. Clin Chim Acta, 2019, 493: 92-97.
20.	许正锯, 潘兴南, 魏梅娟, 等. 慢性乙型肝炎病毒感染者恩替卡韦抗病毒治疗前后血清高尔基体蛋白 GP73 的变化. 中华实验和临床感染病杂志(电子版), 2016, 10(3): 298-303.
21.	Liu L, Zhu J, Yang J, et al. GP73 facilitates hepatitis B virus replication by repressing the NF-κB signaling pathway. J Med Virol, 2020: 20.
22.	刘亚萍, 赵倩, 殷燕, 等. 慢性乙型肝炎患者血清 GP73、HA 水平与 HBV DNA 载量及肝功能的相关性研究. 临床误诊误治, 2019, 32(9): 48-53.
23.	Deveci O, Kaplan I, Tekin R, et al. Prognostic value of Golgi P73 and beta 2-microglobulin in patients with viral hepatitis B. Acta Biochim Pol, 2020, 67(1): 7-14.
24.	马玲玉, 甄一宁, 罗云萍, 等. gp73 在小鼠肝纤维化肝组织中的表达及机制. 基础医学与临床, 2020, 40(6): 771-776.
25.	罗双艳, 何颖. 慢性乙肝患者肝脏炎症及纤维化的影响因素及其与血清高尔基体蛋白 73 的相关性. 医学信息, 2021, 34(15): 5-8.
26.	姚明解, 王雷婕, 关贵文, 等. 血清高尔基体蛋白 73 在辅助诊断慢性乙型肝炎患者中度以上肝损伤中的应用. 临床肝胆病杂志, 2018, 34(4): 755-759.
27.	包海林, 谢群. HBV DNA、AFP、GP73 在慢性乙型肝炎病情严重程度及肝纤维化诊断中的应用价值研究. 海南医学院学报, 2019, 25(9): 700-703.
28.	潘俊均, 黄仙圣, 岑伟明, 等. 不同病毒载量慢性乙型肝炎患者血清 AFP 与 GGT 和 GP73 变化及其临床意义. 热带医学杂志, 2022, 22(2): 179-183.
29.	申文晓. 慢性 HBV 感染者血清 GP73 和 IL-6 水平与肝纤维化指标的相关性. 桂林: 桂林医学院, 2019.
30.	王利公, 赵珊, 陶慧, 等. 血清 AFP、GP73 和 AFP-L3 联合检测在慢性乙型肝炎诊断中的价值. 国际检验医学杂志, 2019, 40(21): 2625-2628, 2632.
31.	杜婷. 血清高尔基体蛋白 73 对 ALT 正常或轻度升高的慢性乙型肝炎病毒感染者肝脏病变的预测价值. 银川: 宁夏医科大学, 2021.
32.	胡蕾蕾. 血清指标在慢性乙型肝炎患者肝纤维化诊断中的应用价值. 医药论坛杂志, 2021, 42(22): 43-46.
33.	王磊. 血清 SF、RBP4、GP73、resistin 水平检测在慢性乙型肝炎患者病情评估中的应用价值. 实验与检验医学, 2018, 36(5): 752-754.
34.	奚经巧, 林枝, 赵春, 等. 肝功能正常慢性乙肝患者肝组织 GP73 表达与纤维化及炎症分级关系. 实用预防医学, 2018, 25(9): 1125-1128.
35.	黄冠华. 血清 GP73、CTLA4 水平与慢性乙型肝炎患者肝纤维化程度的相关性. 中国实用医刊, 2021, 48(14): 49-52.
36.	Yang D, Yao M, Yan Y, et al. Deoxycholic acid upregulates serum Golgi protein 73 through activating NF-κB pathway and destroying Golgi structure in liver disease. Biomolecules, 2021, 11(2): 205.
37.	鲁凤民, 曾婉嘉, 文夏杰, 等. 慢性乙型肝炎抗病毒治疗相关新型标志物及其临床应用. 肝脏, 2019, 24(5): 483-486.
38.	范旭, 单珊, 刘立伟, 等. 血清高尔基糖蛋白 73 优于 APRI、FIB-4 对慢性 HBV 感染患者显著纤维化的诊断. 现代消化及介入诊疗, 2020, 25(4): 529-532.
39.	Cao Z, Li Z, Wang Y, et al. Assessment of serum Golgi protein 73 as a biomarker for the diagnosis of significant fibrosis in patients with chronic HBV infection. J Viral Hepat, 2017, 24(Suppl 1): 57-65.
40.	Gatselis NK, Tornai T, Shums Z, et al. Golgi protein-73: a biomarker for assessing cirrhosis and prognosis of liver disease patients. World J Gastroenterol, 2020, 26(34): 5130-5145.
41.	马世河, 刘文艳, 陈冲, 等. 血清 GP73 水平联合腹部超声检查对慢性乙型肝炎肝纤维化程度的评估价值. 山东医药, 2022, 62(1): 25-29.
42.	Wei M, Xu Z, Pan X, et al. Serum GP73 - an additional biochemical marker for liver inflammation in chronic HBV infected patients with normal or slightly raised ALT. Sci Rep, 2019, 9(1): 1170.
43.	姜娜, 李瑛, 王光东, 等. 慢性乙肝不同炎症分级患者的肝功能、纤维化指标和 GP73 检测及临床意义. 海南医学, 2019, 30(24): 3155-3158.
44.	许正锯, 潘兴南, 魏梅娟, 等. 慢性 HBV 感染者血清 GP73 水平与白细胞介素 6 含量的相关性. 肝脏, 2017, 22(2): 136-139.
45.	刘沁雨, 常越, 张文, 等. GP73 预测慢性乙型肝炎患者肝硬化进展研究. 武警医学, 2020, 31(4): 317-323.
46.	Liu T, Yao M, Liu S, et al. Serum Golgi protein 73 is not a suitable diagnostic marker for hepatocellular carcinoma. Oncotarget, 2017, 8(10): 16498-16506.
47.	Yao M, Wang L, Leung PSC, et al. The clinical significance of GP73 in immunologically mediated chronic liver diseases: experimental data and literature review. Clin Rev Allergy Immunol, 2018, 54(2): 282-294.
48.	Atilla A, Taşkın MH, Kazak Z, et al. GP73 level in patients with chronic hepatitis B: relationship with liver biopsy, levels of ALT, AST and HBV DNA. Indian J Pathol Microbiol, 2022, 65(1): 55-58.
49.	刘燕娜, 姚明解, 郑素军, 等. 血清高尔基体蛋白 73 在慢性肝病患者中的临床应用. 中华肝脏病杂志, 2022, 30(1): 4-8.
50.	魏丰贤, 刘钊, 耿婕, 等. 高尔基体蛋白 73 与肝脏疾病的关系. 临床肝胆病杂志, 2017, 33(8): 1595-1598.
51.	黎振威. 高尔基体蛋白 73 表达对 HBV 感染慢性肝病患者抗病毒治疗后肝纤维化改善的预测价值. 银川: 宁夏医科大学, 2019.
52.	党英男, 贾舒婷, 赵伟, 等. 慢性乙型肝炎患者血清 IL-17A、GP73 水平与肝功能指标及病情严重程度的关系分析. 现代生物医学进展, 2020, 20(23): 4580-4584, 4570.
53.	程华, 鞠辉, 宋德顺, 等. 慢性乙型肝炎患者血清血管生成素样蛋白 2 和高尔基体蛋白 73 水平变化及其诊断显著肝纤维化的效能分析. 实用肝脏病杂志, 2019, 22(4): 494-497.
54.	Xia Y, Zhang Y, Shen M, et al. Golgi protein 73 and its diagnostic value in liver diseases. Cell Prolif, 2019, 52(2): e12538.

1. Kladney RD, Bulla GA, Guo L, et al. GP73, a novel Golgi-localized protein upregulated by viral infection. Gene, 2000, 249(1/2): 53-65.
2. Rosa-Ferreira C, Christis C, Torres IL, et al. The small G protein Arl5 contributes to endosome-to-Golgi traffic by aiding the recruitment of the GARP complex to the Golgi. Biol Open, 2015, 4(4): 474-481.
3. Cao Z, Li Z, Wang H, et al. Algorithm of Golgi protein 73 and liver stiffness accurately diagnoses significant fibrosis in chronic HBV infection. Liver Int, 2017, 37(11): 1612-1621.
4. Block TM, Comunale MA, Lowman M, et al. Use of targeted glycoproteomics to identify serum glycoproteins that correlate with liver cancer in woodchucks and humans. Proc Natl Acad Sci U S A, 2005, 102(3): 779-784.
5. Gatselis NK, Zachou K, Giannoulis G, et al. Serum cartilage oligomeric matrix protein and Golgi protein-73: new diagnostic and predictive tools for liver fibrosis and hepatocellular cancer?. Cancers (Basel), 2021, 13(14): 3510.
6. Dong M, Chen ZH, Li X, et al. Serum Golgi protein 73 is a prognostic rather than diagnostic marker in hepatocellular carcinoma. Oncol Lett, 2017, 14(5): 6277-6284.
7. Liang R, Liu Z, Piao X, et al. Research progress on GP73 in malignant tumors. Onco Targets Ther, 2018, 11: 7417-7421.
8. 田霞. 血清 GDF-15、GP73、AFP 对肝细胞癌的诊断价值研究. 检验医学与临床, 2021, 18(16): 2438-2440.
9. 潘俊均, 黄仙圣, 岑伟明, 等. AFP、AFP-L3%、DCP 与 GP73 联合检测辅助诊断肝炎、肝癌临床价值. 分子诊断与治疗杂志, 2021, 13(10): 1579-1582.
10. 林召, 党小军, 侯智辉, 等. 血清 FFA、GP73 水平变化与慢性乙型肝炎患者病情程度的关联性及临床意义探讨. 泰山医学院学报, 2018, 39(8): 921-923.
11. 贾芳岩, 佘亚辉, 余明杰, 等. 慢性乙型肝炎患者血清 AFP-L3、GP73、AFP 水平变化及临床价值研究. 国际检验医学杂志, 2020, 41(12): 1527-1529.
12. 郑志恒, 李维筠, 回振宇, 等. 聚乙二醇干扰素α-2a 联合恩替卡韦治疗慢性乙型肝炎患者疗效及血清 Pygo2 和 GP73 水平变化. 实用肝脏病杂志, 2021, 24(1): 19-22.
13. Peng Y, Zeng Q, Wan L, et al. GP73 is a TBC-domain Rab GTPase-activating protein contributing to the pathogenesis of non-alcoholic fatty liver disease without obesity. Nat Commun, 2021, 12(1): 7004.
14. Wang L, Yao M, Liu S, et al. Serum Golgi protein 73 as a potential biomarker for hepatic necroinflammation in population with nonalcoholic steatohepatitis. Dis Markers, 2020, 2020: 6036904.
15. Xu Z, Shen J, Pan X, et al. Predictive value of serum Golgi protein 73 for prominent hepatic necroinflammation in chronic HBV infection. J Med Virol, 2018, 90(6): 1053-1062.
16. 张晓坤, 司徒瑞儒. 甲胎蛋白、甲胎蛋白异质体 3 比率、高尔基体蛋白 73 联合检测在原发性肝癌诊断中的价值. 实用医学杂志, 2021, 37(8): 1068-1071.
17. 袁吉磊, 黄辉, 成强. 血清前白蛋白联合高尔基体蛋白 73 在肝病检测及治疗过程中的应用. 中国社区医师, 2017, 33(3): 108-109.
18. 向琴. 血清 GP73 在 HBV 感染的慢性重型肝炎患者的表达水平及其对短期预后的预测价值. 南充: 川北医学院, 2018.
19. Yao M, Wang L, You H, et al. Serum GP73 combined AST and GGT reflects moderate to severe liver inflammation in chronic hepatitis B. Clin Chim Acta, 2019, 493: 92-97.
20. 许正锯, 潘兴南, 魏梅娟, 等. 慢性乙型肝炎病毒感染者恩替卡韦抗病毒治疗前后血清高尔基体蛋白 GP73 的变化. 中华实验和临床感染病杂志(电子版), 2016, 10(3): 298-303.
21. Liu L, Zhu J, Yang J, et al. GP73 facilitates hepatitis B virus replication by repressing the NF-κB signaling pathway. J Med Virol, 2020: 20.
22. 刘亚萍, 赵倩, 殷燕, 等. 慢性乙型肝炎患者血清 GP73、HA 水平与 HBV DNA 载量及肝功能的相关性研究. 临床误诊误治, 2019, 32(9): 48-53.
23. Deveci O, Kaplan I, Tekin R, et al. Prognostic value of Golgi P73 and beta 2-microglobulin in patients with viral hepatitis B. Acta Biochim Pol, 2020, 67(1): 7-14.
24. 马玲玉, 甄一宁, 罗云萍, 等. gp73 在小鼠肝纤维化肝组织中的表达及机制. 基础医学与临床, 2020, 40(6): 771-776.
25. 罗双艳, 何颖. 慢性乙肝患者肝脏炎症及纤维化的影响因素及其与血清高尔基体蛋白 73 的相关性. 医学信息, 2021, 34(15): 5-8.
26. 姚明解, 王雷婕, 关贵文, 等. 血清高尔基体蛋白 73 在辅助诊断慢性乙型肝炎患者中度以上肝损伤中的应用. 临床肝胆病杂志, 2018, 34(4): 755-759.
27. 包海林, 谢群. HBV DNA、AFP、GP73 在慢性乙型肝炎病情严重程度及肝纤维化诊断中的应用价值研究. 海南医学院学报, 2019, 25(9): 700-703.
28. 潘俊均, 黄仙圣, 岑伟明, 等. 不同病毒载量慢性乙型肝炎患者血清 AFP 与 GGT 和 GP73 变化及其临床意义. 热带医学杂志, 2022, 22(2): 179-183.
29. 申文晓. 慢性 HBV 感染者血清 GP73 和 IL-6 水平与肝纤维化指标的相关性. 桂林: 桂林医学院, 2019.
30. 王利公, 赵珊, 陶慧, 等. 血清 AFP、GP73 和 AFP-L3 联合检测在慢性乙型肝炎诊断中的价值. 国际检验医学杂志, 2019, 40(21): 2625-2628, 2632.
31. 杜婷. 血清高尔基体蛋白 73 对 ALT 正常或轻度升高的慢性乙型肝炎病毒感染者肝脏病变的预测价值. 银川: 宁夏医科大学, 2021.
32. 胡蕾蕾. 血清指标在慢性乙型肝炎患者肝纤维化诊断中的应用价值. 医药论坛杂志, 2021, 42(22): 43-46.
33. 王磊. 血清 SF、RBP4、GP73、resistin 水平检测在慢性乙型肝炎患者病情评估中的应用价值. 实验与检验医学, 2018, 36(5): 752-754.
34. 奚经巧, 林枝, 赵春, 等. 肝功能正常慢性乙肝患者肝组织 GP73 表达与纤维化及炎症分级关系. 实用预防医学, 2018, 25(9): 1125-1128.
35. 黄冠华. 血清 GP73、CTLA4 水平与慢性乙型肝炎患者肝纤维化程度的相关性. 中国实用医刊, 2021, 48(14): 49-52.
36. Yang D, Yao M, Yan Y, et al. Deoxycholic acid upregulates serum Golgi protein 73 through activating NF-κB pathway and destroying Golgi structure in liver disease. Biomolecules, 2021, 11(2): 205.
37. 鲁凤民, 曾婉嘉, 文夏杰, 等. 慢性乙型肝炎抗病毒治疗相关新型标志物及其临床应用. 肝脏, 2019, 24(5): 483-486.
38. 范旭, 单珊, 刘立伟, 等. 血清高尔基糖蛋白 73 优于 APRI、FIB-4 对慢性 HBV 感染患者显著纤维化的诊断. 现代消化及介入诊疗, 2020, 25(4): 529-532.
39. Cao Z, Li Z, Wang Y, et al. Assessment of serum Golgi protein 73 as a biomarker for the diagnosis of significant fibrosis in patients with chronic HBV infection. J Viral Hepat, 2017, 24(Suppl 1): 57-65.
40. Gatselis NK, Tornai T, Shums Z, et al. Golgi protein-73: a biomarker for assessing cirrhosis and prognosis of liver disease patients. World J Gastroenterol, 2020, 26(34): 5130-5145.
41. 马世河, 刘文艳, 陈冲, 等. 血清 GP73 水平联合腹部超声检查对慢性乙型肝炎肝纤维化程度的评估价值. 山东医药, 2022, 62(1): 25-29.
42. Wei M, Xu Z, Pan X, et al. Serum GP73 - an additional biochemical marker for liver inflammation in chronic HBV infected patients with normal or slightly raised ALT. Sci Rep, 2019, 9(1): 1170.
43. 姜娜, 李瑛, 王光东, 等. 慢性乙肝不同炎症分级患者的肝功能、纤维化指标和 GP73 检测及临床意义. 海南医学, 2019, 30(24): 3155-3158.
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Research progress of novel serum marker Golgi protein 73 in clinical diagnosis and treatment of chronic hepatitis B

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