肝癌特异性GGT诊断肝癌的研究进展
沈卫东, 黄介飞, 南通大学附属医院消化内科 江苏省南通市 226001
通讯作者:沈卫东, 226001, 江苏省南通市西寺路20号, 南通大学附属医院消化内科. shenwd2003@yahoo.com.cn
电话: 0513-5052078
收稿日期: 2005-03-06 接受日期: 2005-04-01
摘要
g-谷氨酰转移酶(gamma-glutamyltransferase ，GGT)及其同工酶作为肝癌的标记物日益受到重视，GGT-Ⅱ已成为AFP以外的最佳肝癌标志物，并在检测方法和临床应用等方面有了较多新的进展.本文就GGT基因的分子结构和基因构成、肝内分布特点及肝癌时的异常表达机制、检测及临床价值等作一综述.
, http://www.100md.com
沈卫东, 黄介飞. 肝癌特异性GGT诊断肝癌的研究进展. 世界华人消化杂志 2005;13(9):1119-11221 Fujiyama S, Tanaka M, Maeda S, Ashihara H, Hirata R, Tomita K. Tumor markers in early diagnosis , follow-up
and management of patients with hepatocellular carcinoma. Oncology 2002;62:57-63
2 Tang ZY. Hepatocellular carcinoma-Cause, treatment and metastasis. World J Gastroenterol 2001;7:542-546
3 Parks R, Garden O. Liver resection for cancer. World J Gastroenterol 2001;7:766-771
, 百拇医药
4 Yamashita K, Totani K, Iwaki Y, Takamisawa I, Tateishi N, Higashi T, Sakamoto Y, Kobata A. Compsrative study of the
sugar chains of gamma-glutamyltranspeptidases purified from human hepatocellular carcinoma and from human liver.
J Biochem (Tokyo) 1989;105:728-735
5 Pettersen I, Andersen JH, Bjornland K, Mathisen O, Bremnes R, Wellman M, Visvikis A, Huseby NE. Heterogeneity in
, http://www.100md.com
gamma-glutamyltransferase mRNA expression and glycan structures. Search for tumor-specific variants in human
liver metastases and colon carcinoma cells. Biochim Biophys Acta 2003;1648:210-218
6 Courtay C, Heisterkamp N, Siest G, Groffen J. Expression of multiple g-glutamyltransferase genes in man.
Biochem J 1994;297(Pt 3):503-508
7 Visvikis A, Pawlak A, Accaoui MJ, Ichino K, Leh H, Guellaen G, Wellman M. Structure of the 5' sequences of the
, 百拇医药
human gamma-glutamyltransferase gene. Eur J Biochem 2001;268:317-325
8 Holic N, Suzuki T, Corlu A, Couchie D, Chobert MN, Guguen-Guillouzo C, Laperche Y. Differential expression of the
rat gamma-glutamyl transpeptidase gene promoters along with differentiation of hepatoblasts into biliary or hepatocytic
lineage. Am J Pathol 2000;157:537-548
9 Mikkelsen IM, Mortensen B, Laperche Y, Huseby NE. The expression of gamma-glutamyltransferase in rat colon
, 百拇医药
carcinoma cells is distinctly regulated during differentiation and oxidative stress. Mol Cell Biochem 2002;232:87-95
10 Ha WS, Kim CK, Song SH, Kang CB. Study on mechanism of multistep hepatotumorigenesis in rat: development of
hepatotumorigenesis. J Vet Sci 2001;2:53-58
11 Ohata M, Toda G. Gamma-glutamyltranspeptidase (Gamma-GT). Rinsho Byori 2001;116(Suppl):62-71
, http://www.100md.com
12 Hochwald SN, Harriosn LE, Rose DM, Anderson M, Burt ME. Gamma-glutamyl transpeptidase mediation of
tumor gluta-thione utilization in vivo. J Natl Cancer Inst 1996;88:193-197
13 Lee DH, Blomhoff R, Jacobs DR Jr. Is serum gamma glutamy-ltransferase a marker of oxidative stress?
Free Radic Res 2004;38:535-539
14 Yao D, Jiang D, Huang Z, Lu J, Tao Q, Yu Z, Meng X. Abnormal expression of hepatoma specific gamma-glutamyl
, http://www.100md.com
transferase and alteration of gamma-glutamyl transferase gene methylation status in patients with hepatocellular
carcinoma. Cancer 2000;88:761-769
15 Orlowski M, Szczeklik A. Heterogeneity of serum gamma-glutamyl transpeptidase in hepatobiliary diseases.
Clin Chim Acta 1967;15:387-391
16 Xu KC, Meng XY, Shi YC, Ge ZJ, Ye L, Yu ZJ, Yang DM. The diagnostic value of a hepatoma-specific band of serum
, http://www.100md.com
gamma-glutamyl transferase. Int J Cancer 1985;36:667-669
17 Xu K, Meng XY, Wu JW, Shen B, Shi YC, Wei Q. Diagnostic value of serum gamma-glutamyl transferase isoenzyme
for hepatocellular carcinoma: a 10-year study. Am J Gastroenterol 1992;87:991-995
18 沈鼎明, 沈薇, 左国庆, 曾维政, 梅浙川, 周友梅, 徐葆元. 血清肝癌标志物在原发性肝癌诊断中
的价值-附321例肝癌测定结果. 中华消化杂志 1992;12:223-226
, http://www.100md.com
19 黄介飞, 姚登福, 孟铣镛, 魏群, 倪润洲, 张弘, 肖明兵. 肝癌特异性GGT火箭电泳对原发性肝癌的诊断价值.
中华消化杂志 1995;15:269-271
20 Stolzel U, Teubner A, Ernstberger J, Habeck JO, Schuppan D.Isolatedelevation of gGT:What should be the diagnostic
approach? Dtsch Med Wochenschr 2004;129(Suppl 2):S54-56
21 苗爱莲, 李军, 魏曙亚, 候蓉, 原荣, 王香林. 肝癌特异g-谷氨酰转肽酶同功酶Ⅱ活性检测及其临床价值.
西安交通大学学报(医学版) 2003;24:85-87
, http://www.100md.com
22 Ni RZ, Huang JF, Xiao MB, Zhang PY, Meng XY. Detection of GGT-II byDot-ELISA with monoclonal antibody in the
diagnosis of hepatocellularcarcinoma. Ai Zheng 2004;23:66-68
23 Tang W, Wang XY, Gao JE, Ji HP, Tao QM, Ji Y. Preparation andapplication of the monoclonal antibody against
hepatoma-specific gamma-glutamyltransferase.Zhonghua Ganzangbing Zazhi 2003;11:100-102
, 百拇医药
24 Yao DF, Huang ZW, Chen SZ, Huang JF, Lu JX, Xiao MB, Meng XY.Diagnosis of hepatocellular carcinoma by
quantitative detection of hepatoma-specificbands of serum gamma-glutamyltransferase. Am J Clin Pathol
1998;110:743-749
25 于嘉屏, 王爱华, 顾鹏飞, 陈军. 免疫沉淀法测定血清中与两种脂蛋白结合的g-谷氨酰基转移酶活性及
其诊断肝癌的价值. 中华检验医学杂志 2003;26:371-373
26 Pompili M, Addolorato G, Pignataro G, Rossi C, Zuppi C, Covino M,Grieco A, Gasbarrini G, Rapaccini GL. Evaluation of
, 百拇医药
the albumin-gamma-glutamyltransferaseisoenzyme as a diagnostic marker of hepatocellular carcinoma-complicating
liver cirrhosis. J GastroenterolHepatol 2003;18:288-295
27 司维柯, 李士敏, 罗朝学, 胡国珍, 何长生, 王源, 魏明竞. 伴刀豆球蛋白A识别正常与肝癌g-谷氨酰转移
酶的实验观察. 第三军医大学学报 2000;22:294-295
28 Tsutsumi M, Sakamuro D, Takada A, Zang SC, Furukawa T,Taniguchi N.Detection of a unique gamma
, http://www.100md.com
-glutamyl-transpeptidase messengerRNA species closely related to the development of hepatocellular carcinomain
humans:a new candidate for earlydiagnosis of hepatocellular carcinoma. Hepatology 1996;23:1093-1097
29 Daubeuf S, Accaoui MJ, Pettersen I, Huseby NE, Visvikis A, GalteauMM. Differential regulation of
gamma-glutamy-ltransferase mRNAs infour human tumour cell lines. Biochim Biophys Acta 2001;1568:67-73
, 百拇医药
30 Jeng KS, Sheen IS, Tsai YC. Gamma-glutamyl transpeptidase messengerRNA may serve as a diagnostic aid in
hepatocellular carcinoma. Br JSurg 2001;88:986-987
31 Sheen IS, Jeng KS, Tsai YC. Is the expression of g-glutamyl transpeptidasemessenger RNA an indicator of biological
behavior in recurrent hepatocellularcarcinoma? World J Gastroenterol 2003;9:468-473
, 百拇医药
32 Han GQ, Qin CY, Shu RH. The analysis of gamma-glutamyl transferasegene in different type liver tissues.
World J Gastroenterol 2003;9:276-280
33 Han GQ, Qin CY, Ren WH, Shi J, Wang YJ, Liu HL. Clinical impact ofgamma-glutamyl transpeptidase messenger RNA
subtypes on early diagnosis ofhepatocellular carcinoma. Ai Zheng 2002;21:192-195
34 秦成坤, 彭志海, 韩国庆. 外周血g-谷氨酰转移酶mRNA-H亚型与甲胎蛋白对原发性肝癌诊断及
肝外转移意义的比较. 中华实验外科杂志 2004;21:671-672
编辑 张海宁, 百拇医药( 沈卫东,黄介飞)
通讯作者:沈卫东, 226001, 江苏省南通市西寺路20号, 南通大学附属医院消化内科. shenwd2003@yahoo.com.cn
电话: 0513-5052078
收稿日期: 2005-03-06 接受日期: 2005-04-01
摘要
g-谷氨酰转移酶(gamma-glutamyltransferase ，GGT)及其同工酶作为肝癌的标记物日益受到重视，GGT-Ⅱ已成为AFP以外的最佳肝癌标志物，并在检测方法和临床应用等方面有了较多新的进展.本文就GGT基因的分子结构和基因构成、肝内分布特点及肝癌时的异常表达机制、检测及临床价值等作一综述.
, http://www.100md.com
沈卫东, 黄介飞. 肝癌特异性GGT诊断肝癌的研究进展. 世界华人消化杂志 2005;13(9):1119-11221 Fujiyama S, Tanaka M, Maeda S, Ashihara H, Hirata R, Tomita K. Tumor markers in early diagnosis , follow-up
and management of patients with hepatocellular carcinoma. Oncology 2002;62:57-63
2 Tang ZY. Hepatocellular carcinoma-Cause, treatment and metastasis. World J Gastroenterol 2001;7:542-546
3 Parks R, Garden O. Liver resection for cancer. World J Gastroenterol 2001;7:766-771
, 百拇医药
4 Yamashita K, Totani K, Iwaki Y, Takamisawa I, Tateishi N, Higashi T, Sakamoto Y, Kobata A. Compsrative study of the
sugar chains of gamma-glutamyltranspeptidases purified from human hepatocellular carcinoma and from human liver.
J Biochem (Tokyo) 1989;105:728-735
5 Pettersen I, Andersen JH, Bjornland K, Mathisen O, Bremnes R, Wellman M, Visvikis A, Huseby NE. Heterogeneity in
, http://www.100md.com
gamma-glutamyltransferase mRNA expression and glycan structures. Search for tumor-specific variants in human
liver metastases and colon carcinoma cells. Biochim Biophys Acta 2003;1648:210-218
6 Courtay C, Heisterkamp N, Siest G, Groffen J. Expression of multiple g-glutamyltransferase genes in man.
Biochem J 1994;297(Pt 3):503-508
7 Visvikis A, Pawlak A, Accaoui MJ, Ichino K, Leh H, Guellaen G, Wellman M. Structure of the 5' sequences of the
, 百拇医药
human gamma-glutamyltransferase gene. Eur J Biochem 2001;268:317-325
8 Holic N, Suzuki T, Corlu A, Couchie D, Chobert MN, Guguen-Guillouzo C, Laperche Y. Differential expression of the
rat gamma-glutamyl transpeptidase gene promoters along with differentiation of hepatoblasts into biliary or hepatocytic
lineage. Am J Pathol 2000;157:537-548
9 Mikkelsen IM, Mortensen B, Laperche Y, Huseby NE. The expression of gamma-glutamyltransferase in rat colon
, 百拇医药
carcinoma cells is distinctly regulated during differentiation and oxidative stress. Mol Cell Biochem 2002;232:87-95
10 Ha WS, Kim CK, Song SH, Kang CB. Study on mechanism of multistep hepatotumorigenesis in rat: development of
hepatotumorigenesis. J Vet Sci 2001;2:53-58
11 Ohata M, Toda G. Gamma-glutamyltranspeptidase (Gamma-GT). Rinsho Byori 2001;116(Suppl):62-71
, http://www.100md.com
12 Hochwald SN, Harriosn LE, Rose DM, Anderson M, Burt ME. Gamma-glutamyl transpeptidase mediation of
tumor gluta-thione utilization in vivo. J Natl Cancer Inst 1996;88:193-197
13 Lee DH, Blomhoff R, Jacobs DR Jr. Is serum gamma glutamy-ltransferase a marker of oxidative stress?
Free Radic Res 2004;38:535-539
14 Yao D, Jiang D, Huang Z, Lu J, Tao Q, Yu Z, Meng X. Abnormal expression of hepatoma specific gamma-glutamyl
, http://www.100md.com
transferase and alteration of gamma-glutamyl transferase gene methylation status in patients with hepatocellular
carcinoma. Cancer 2000;88:761-769
15 Orlowski M, Szczeklik A. Heterogeneity of serum gamma-glutamyl transpeptidase in hepatobiliary diseases.
Clin Chim Acta 1967;15:387-391
16 Xu KC, Meng XY, Shi YC, Ge ZJ, Ye L, Yu ZJ, Yang DM. The diagnostic value of a hepatoma-specific band of serum
, http://www.100md.com
gamma-glutamyl transferase. Int J Cancer 1985;36:667-669
17 Xu K, Meng XY, Wu JW, Shen B, Shi YC, Wei Q. Diagnostic value of serum gamma-glutamyl transferase isoenzyme
for hepatocellular carcinoma: a 10-year study. Am J Gastroenterol 1992;87:991-995
18 沈鼎明, 沈薇, 左国庆, 曾维政, 梅浙川, 周友梅, 徐葆元. 血清肝癌标志物在原发性肝癌诊断中
的价值-附321例肝癌测定结果. 中华消化杂志 1992;12:223-226
, http://www.100md.com
19 黄介飞, 姚登福, 孟铣镛, 魏群, 倪润洲, 张弘, 肖明兵. 肝癌特异性GGT火箭电泳对原发性肝癌的诊断价值.
中华消化杂志 1995;15:269-271
20 Stolzel U, Teubner A, Ernstberger J, Habeck JO, Schuppan D.Isolatedelevation of gGT:What should be the diagnostic
approach? Dtsch Med Wochenschr 2004;129(Suppl 2):S54-56
21 苗爱莲, 李军, 魏曙亚, 候蓉, 原荣, 王香林. 肝癌特异g-谷氨酰转肽酶同功酶Ⅱ活性检测及其临床价值.
西安交通大学学报(医学版) 2003;24:85-87
, http://www.100md.com
22 Ni RZ, Huang JF, Xiao MB, Zhang PY, Meng XY. Detection of GGT-II byDot-ELISA with monoclonal antibody in the
diagnosis of hepatocellularcarcinoma. Ai Zheng 2004;23:66-68
23 Tang W, Wang XY, Gao JE, Ji HP, Tao QM, Ji Y. Preparation andapplication of the monoclonal antibody against
hepatoma-specific gamma-glutamyltransferase.Zhonghua Ganzangbing Zazhi 2003;11:100-102
, 百拇医药
24 Yao DF, Huang ZW, Chen SZ, Huang JF, Lu JX, Xiao MB, Meng XY.Diagnosis of hepatocellular carcinoma by
quantitative detection of hepatoma-specificbands of serum gamma-glutamyltransferase. Am J Clin Pathol
1998;110:743-749
25 于嘉屏, 王爱华, 顾鹏飞, 陈军. 免疫沉淀法测定血清中与两种脂蛋白结合的g-谷氨酰基转移酶活性及
其诊断肝癌的价值. 中华检验医学杂志 2003;26:371-373
26 Pompili M, Addolorato G, Pignataro G, Rossi C, Zuppi C, Covino M,Grieco A, Gasbarrini G, Rapaccini GL. Evaluation of
, 百拇医药
the albumin-gamma-glutamyltransferaseisoenzyme as a diagnostic marker of hepatocellular carcinoma-complicating
liver cirrhosis. J GastroenterolHepatol 2003;18:288-295
27 司维柯, 李士敏, 罗朝学, 胡国珍, 何长生, 王源, 魏明竞. 伴刀豆球蛋白A识别正常与肝癌g-谷氨酰转移
酶的实验观察. 第三军医大学学报 2000;22:294-295
28 Tsutsumi M, Sakamuro D, Takada A, Zang SC, Furukawa T,Taniguchi N.Detection of a unique gamma
, http://www.100md.com
-glutamyl-transpeptidase messengerRNA species closely related to the development of hepatocellular carcinomain
humans:a new candidate for earlydiagnosis of hepatocellular carcinoma. Hepatology 1996;23:1093-1097
29 Daubeuf S, Accaoui MJ, Pettersen I, Huseby NE, Visvikis A, GalteauMM. Differential regulation of
gamma-glutamy-ltransferase mRNAs infour human tumour cell lines. Biochim Biophys Acta 2001;1568:67-73
, 百拇医药
30 Jeng KS, Sheen IS, Tsai YC. Gamma-glutamyl transpeptidase messengerRNA may serve as a diagnostic aid in
hepatocellular carcinoma. Br JSurg 2001;88:986-987
31 Sheen IS, Jeng KS, Tsai YC. Is the expression of g-glutamyl transpeptidasemessenger RNA an indicator of biological
behavior in recurrent hepatocellularcarcinoma? World J Gastroenterol 2003;9:468-473
, 百拇医药
32 Han GQ, Qin CY, Shu RH. The analysis of gamma-glutamyl transferasegene in different type liver tissues.
World J Gastroenterol 2003;9:276-280
33 Han GQ, Qin CY, Ren WH, Shi J, Wang YJ, Liu HL. Clinical impact ofgamma-glutamyl transpeptidase messenger RNA
subtypes on early diagnosis ofhepatocellular carcinoma. Ai Zheng 2002;21:192-195
34 秦成坤, 彭志海, 韩国庆. 外周血g-谷氨酰转移酶mRNA-H亚型与甲胎蛋白对原发性肝癌诊断及
肝外转移意义的比较. 中华实验外科杂志 2004;21:671-672
编辑 张海宁, 百拇医药( 沈卫东,黄介飞)
