与胃癌相关的血清学肿瘤标志物的研究进展
白雪蕾,袁媛,中国医科大学附属第一医院肿瘤研究所 辽宁省沈阳市 110001
国家十五科技攻关项目资助课题,No. 2004BA703B04-02
通讯作者:袁媛,110001, 辽宁省沈阳市和平区南京北街155号,中国医科大学附属第一医院肿瘤研究所. yyuan@mail.cmu.edu.cn
电话:024-23256666-6153 传真:024-22703576
收稿日期:2005-04-26 接受日期:2005-05-14
摘要
胃癌是严重威胁人类健康的恶性肿瘤之一，其防治有赖于早期发现及选择合适的治疗方案，寻找特异性肿瘤标志物对以上两方面均有重要作用，其中血清学肿瘤标志物以其特殊的优势成为众多学者研究的重点.近年来学者们针对胃癌血清学肿瘤标志物，包括基因、蛋白水平，作了详细的研究.这些血清学肿瘤标志物对于胃癌的早期诊断、组织分型及判断预后等都有重要意义.本文分别叙述了基因、抗原及抗体、酶及同工酶、激素等肿瘤标志物，尤其针对当前研究的热点问题-循环DNA，总结了其定量及定性改变的意义.文章分析了各个肿瘤标志物的基础研究及临床用途，并指出了当前胃癌血清学肿瘤标志物检测中存在的问题及可行的解决途径.
, 百拇医药
白雪蕾, 袁媛. 与胃癌相关的血清学肿瘤标志物的研究进展. 世界华人消化杂志 2005;13(12):1440-1444
Laktionov PP, Tamkovich SN, Rykova EY, Bryzgunova OE, Starikov AV,Kuznetsova NP, Sumarokov SV, Kolomiets
SA, Sevostianova NV, Vlassov VV.Extracellular circulating nucleic acids in human plasma in health and
disease. Nucleosides Nucleotides NucleicAcids 2004;23:879-883
2 Papadopoulou E, Davilas E, Sotiriou V, Koliopanos A, Aggelakis F,Dardoufas K, Agnanti NJ, Karydas I, Nasioulas
, 百拇医药
G. Cell-free DNA and RNA in plasma as a newmolecular marker for prostate cancer. Oncol Res 2004;14:439-445
3 Tu H, Gao HF, Fu SL, Chen H. Quantitative analysis of circulatingDNA in serum of cancer patients. Zhonghua
Zhongliu Zazhi 2004;26:606-608
4 Leon SA, Shapiro B, Sklaroff DM, Yaros MJ. Free DNA in the serum ofcancer patients and the effect of therapy.
, http://www.100md.com Cancer Res 1977;37:646-650
5 Fujiwara K, Fujimoto N, Tabata M, Nishii K, Matsuo K, Hotta K,Kozuki T, Aoe M, Kiura K, Ueoka H, Tanimoto
M. Identification of epigenetic aberrantpromoter methylation in serum DNA is useful for early detection of lungcancer.
Clin Cancer Res 2005;11:1219-1225
6 Schwarzenbach H, Muller V, Stahmann N, Pantel K. Detection andcharacterization of circulating microsatellite-DNA
, 百拇医药
in blood of patients with breast cancer. AnnN Y Acad Sci 2004;1022:25-32
7 Chu HJ, Heo J, Seo SB, Kim GH, Kang DH, Song GA, Cho M, Yang US.Detection of aberrant p16INK4A methylation in
sera of patients with liver cirrhosis andhepatocellular carcinoma. J Korean Med Sci 2004;19:83-86
8 屠红, 高海峰, 傅士龙, 陈颢. 肿瘤患者循环DNA的定量检测. 中华肿瘤杂志 2004;26:606-608
9 He XS, Rong YH, Su Q, Luo Q, He DM, Li YL, Chen Y. Expression ofp16 gene and Rb protein in gastric carcinoma and
, 百拇医药
their clinicopathological significance. WorldJ Gastroenterol 2005;11:2218-2223
10 Wu M, Semba S, Oue N, Ikehara N, Yasui W, Yokozaki H. BRAF/K-rasmutation, microsatellite instability, and
promoter hypermethylation ofhMLH1/MGMT in human gastric carcinomas. Gastric Cancer 2004;7:246-253
11 Shinmura K, Tao H, Goto M, Igarashi H, Taniguchi T, Maekawa M,Takezaki T, Sugimura H. Inactivating
, 百拇医药
mutations of the human base excisionrepair gene NEIL1 in gastric cancer. Carcinogenesis 2004;25:2311-2317
12 Yashiro M, Nishioka N, Hirakawa K. K-ras mutation influencesmacroscopic features of gastric carcinoma. J Surg
Res 2005;124:74-78
13 Wang JY, Hsieh JS, Chen CC, Tzou WS, Cheng TL, Chen FM, Huang TJ,Huang YS, Huang SY, Yang T, Lin SR.
Alterations of APC, c-met, and p53genes in tumor tissue and serum of patients with gastric cancers. JSurg
, 百拇医药
Res 2004;120:242-248
14 Lee TL, Leung WK, Chan MW, Ng EK, Tong JH, Lo KW, Chung SC, Sung JJ,To KF. Detection of gene
promoter hypermethylation in thetumor and serum of patients with gastric carcinoma. Clin Cancer Res 2002;8:
1761-1766
15 Kanyama Y, Hibi K, Nakayama H, Kodera Y, Ito K, Akiyama S, Nakao A.Detection of p16 promoter hypermethylation
, 百拇医药
in serum of gastric cancer patients. CancerSci 2003;94:418-420
16 Ichikawa D, Koike H, Ikoma H, Ikoma D, Tani N, Otsuji E, KitamuraK, Yamagishi H. Detection of aberrant methylation
as a tumor marker in serum ofpatients with gastric cancer. Anticancer Res 2004;24:2477-2481
17 Tsutsumi S, Kuwano H, Shimura T, Morinaga N, Mochiki E, Asao T.Circulating soluble Fas ligand in patients with
, 百拇医药
gastric carcenoma. Cancer 2000;89:2560-2564
18 Lim SC. Expression of Fas ligand and sFas ligand in human gastricadenocarcinomas. Oncol Rep 2002;9:103-107
19 Ichikura T, Majima T, Uchida T, Okura E, Ogawa T, Mochizuki H.Plasma soluble Fas ligand concentration:
decrease in elderly men and increasein patients with gastric carcinoma. Oncol Rep 2001;8:311-314
, 百拇医药 20 郭冬丽, 宁佩芳, 王兰, 袁媛. 胃癌及癌前状态MG7表达的动态观察及分析. 中华流行病学杂志 2003;6:494-497
21 Ren J, Chen Z, Juan SJ, Yong XY, Pan BR, Fan DM. Detection ofcirculating gastric carcinoma-associated
antigen MG7-Ag in human sera using anestablished single determinant immuno-polymerase chain reaction
technique. Cancer 2000;88:280-285
22 Hyodo I, Doi T, Endo H, Hosokawa Y, Nishikawa Y, Tanimizu M, JinnoK, Kotani Y. Clinical significance of plasma
, 百拇医药
vascular endothelial growth factor ingastrointestinal cancer. Eur J Cancer 1998;34:2041-2045
23 Yoshikawa T, Tsuburaya A, Kobayashi O, Sairenji M, Motohashi H,Yanoma S, Noguchi Y. Plasma concentrations of
VEGF and bFGF in patients withgastric carcinoma. Cancer Lett 2000;153:7-12
24 Ohta M, Konno H, Tanaka T, Baba M, Kamiya K, Syouji T, Kondoh K,Watanabe M, Terada H, Nakamura S.
, http://www.100md.com
The significance of circulatingvascular endothelial growth factor (VEGF)protein in gastric cancer. Cancer
Lett 2003;192:215-225
25 Nakajima K, Suzuli T, Shimada H, Hayashi H, Takeda A, Ochiai T.Detection of preoperative serum anti-p53 antibodies
in gastric cancer. Tumour Biol 1999;20:147-152
26 Miki K, Morita M, Sasajima M, Hoshina R, Kanda E, Urita Y.Usefulness of gastric cancer screening using the
, http://www.100md.com
serum pepsinogen test method. Am JGastroenterol 2003;98:735-739
27 Yahagi N, Miki K, Ichinose M, Kakei N, Matsushima M, Kido M,Shimizu Y, Ishihama S, Tsukada S, Kurokawa K. A
minute gastric cancer detected by anew screening method using serum pepsinogen I and II. Adv Exp Med
Biol 1995;362:145-148
28 Miki K. Serum pepsinogen I/II ratio test. Nippon Rinsho 2003;61:92-95
, http://www.100md.com
29 Urita Y, Hike K, Torii N, Kikuchi Y, Kanda E, Sasajima M, Miki K.Serum pepsinogens as a predicator of the topography
of intestinal metaplasia in patientswith atrophic gastritis. Dig Dis Sci 2004;49:795-801
30 孙丽萍, 宫月华, 袁媛. 血清胃蛋白酶原含量作为幽门螺杆菌除菌疗效判定指标的研究. 世界华人消化杂志 2004;12:
1827-1832
31 赵明, 季晓鹏, 郑永胜. 血清胃泌素对胃溃疡及胃癌的诊断价值. 放射免疫学杂志 2003;16:369-374
, 百拇医药
32 Soran A, Aslar AK, Col C. Are preoperative serum gastrin levelsrelated to resectability and survival in gastric cancer?
Int J Clin Pract 2000;54:652-653
33 Triantafillidis JK, Merikas E, Govosdis V, Konstandellou E,Cheracakis P, Barbatzas C, Tzourmakliotis D, Peros G.
Increased fasting serum levels ofgrowth hormone and gastrin in patients with gastric and large bowel
cancer. Hepatogastroenterology 2003;50(Suppl 2):cclvi-cclx
编辑 王谨晖 审读 张海宁, 百拇医药( 白雪蕾,袁 媛)
国家十五科技攻关项目资助课题,No. 2004BA703B04-02
通讯作者:袁媛,110001, 辽宁省沈阳市和平区南京北街155号,中国医科大学附属第一医院肿瘤研究所. yyuan@mail.cmu.edu.cn
电话:024-23256666-6153 传真:024-22703576
收稿日期:2005-04-26 接受日期:2005-05-14
摘要
胃癌是严重威胁人类健康的恶性肿瘤之一，其防治有赖于早期发现及选择合适的治疗方案，寻找特异性肿瘤标志物对以上两方面均有重要作用，其中血清学肿瘤标志物以其特殊的优势成为众多学者研究的重点.近年来学者们针对胃癌血清学肿瘤标志物，包括基因、蛋白水平，作了详细的研究.这些血清学肿瘤标志物对于胃癌的早期诊断、组织分型及判断预后等都有重要意义.本文分别叙述了基因、抗原及抗体、酶及同工酶、激素等肿瘤标志物，尤其针对当前研究的热点问题-循环DNA，总结了其定量及定性改变的意义.文章分析了各个肿瘤标志物的基础研究及临床用途，并指出了当前胃癌血清学肿瘤标志物检测中存在的问题及可行的解决途径.
, 百拇医药
白雪蕾, 袁媛. 与胃癌相关的血清学肿瘤标志物的研究进展. 世界华人消化杂志 2005;13(12):1440-1444
Laktionov PP, Tamkovich SN, Rykova EY, Bryzgunova OE, Starikov AV,Kuznetsova NP, Sumarokov SV, Kolomiets
SA, Sevostianova NV, Vlassov VV.Extracellular circulating nucleic acids in human plasma in health and
disease. Nucleosides Nucleotides NucleicAcids 2004;23:879-883
2 Papadopoulou E, Davilas E, Sotiriou V, Koliopanos A, Aggelakis F,Dardoufas K, Agnanti NJ, Karydas I, Nasioulas
, 百拇医药
G. Cell-free DNA and RNA in plasma as a newmolecular marker for prostate cancer. Oncol Res 2004;14:439-445
3 Tu H, Gao HF, Fu SL, Chen H. Quantitative analysis of circulatingDNA in serum of cancer patients. Zhonghua
Zhongliu Zazhi 2004;26:606-608
4 Leon SA, Shapiro B, Sklaroff DM, Yaros MJ. Free DNA in the serum ofcancer patients and the effect of therapy.
, http://www.100md.com Cancer Res 1977;37:646-650
5 Fujiwara K, Fujimoto N, Tabata M, Nishii K, Matsuo K, Hotta K,Kozuki T, Aoe M, Kiura K, Ueoka H, Tanimoto
M. Identification of epigenetic aberrantpromoter methylation in serum DNA is useful for early detection of lungcancer.
Clin Cancer Res 2005;11:1219-1225
6 Schwarzenbach H, Muller V, Stahmann N, Pantel K. Detection andcharacterization of circulating microsatellite-DNA
, 百拇医药
in blood of patients with breast cancer. AnnN Y Acad Sci 2004;1022:25-32
7 Chu HJ, Heo J, Seo SB, Kim GH, Kang DH, Song GA, Cho M, Yang US.Detection of aberrant p16INK4A methylation in
sera of patients with liver cirrhosis andhepatocellular carcinoma. J Korean Med Sci 2004;19:83-86
8 屠红, 高海峰, 傅士龙, 陈颢. 肿瘤患者循环DNA的定量检测. 中华肿瘤杂志 2004;26:606-608
9 He XS, Rong YH, Su Q, Luo Q, He DM, Li YL, Chen Y. Expression ofp16 gene and Rb protein in gastric carcinoma and
, 百拇医药
their clinicopathological significance. WorldJ Gastroenterol 2005;11:2218-2223
10 Wu M, Semba S, Oue N, Ikehara N, Yasui W, Yokozaki H. BRAF/K-rasmutation, microsatellite instability, and
promoter hypermethylation ofhMLH1/MGMT in human gastric carcinomas. Gastric Cancer 2004;7:246-253
11 Shinmura K, Tao H, Goto M, Igarashi H, Taniguchi T, Maekawa M,Takezaki T, Sugimura H. Inactivating
, 百拇医药
mutations of the human base excisionrepair gene NEIL1 in gastric cancer. Carcinogenesis 2004;25:2311-2317
12 Yashiro M, Nishioka N, Hirakawa K. K-ras mutation influencesmacroscopic features of gastric carcinoma. J Surg
Res 2005;124:74-78
13 Wang JY, Hsieh JS, Chen CC, Tzou WS, Cheng TL, Chen FM, Huang TJ,Huang YS, Huang SY, Yang T, Lin SR.
Alterations of APC, c-met, and p53genes in tumor tissue and serum of patients with gastric cancers. JSurg
, 百拇医药
Res 2004;120:242-248
14 Lee TL, Leung WK, Chan MW, Ng EK, Tong JH, Lo KW, Chung SC, Sung JJ,To KF. Detection of gene
promoter hypermethylation in thetumor and serum of patients with gastric carcinoma. Clin Cancer Res 2002;8:
1761-1766
15 Kanyama Y, Hibi K, Nakayama H, Kodera Y, Ito K, Akiyama S, Nakao A.Detection of p16 promoter hypermethylation
, 百拇医药
in serum of gastric cancer patients. CancerSci 2003;94:418-420
16 Ichikawa D, Koike H, Ikoma H, Ikoma D, Tani N, Otsuji E, KitamuraK, Yamagishi H. Detection of aberrant methylation
as a tumor marker in serum ofpatients with gastric cancer. Anticancer Res 2004;24:2477-2481
17 Tsutsumi S, Kuwano H, Shimura T, Morinaga N, Mochiki E, Asao T.Circulating soluble Fas ligand in patients with
, 百拇医药
gastric carcenoma. Cancer 2000;89:2560-2564
18 Lim SC. Expression of Fas ligand and sFas ligand in human gastricadenocarcinomas. Oncol Rep 2002;9:103-107
19 Ichikura T, Majima T, Uchida T, Okura E, Ogawa T, Mochizuki H.Plasma soluble Fas ligand concentration:
decrease in elderly men and increasein patients with gastric carcinoma. Oncol Rep 2001;8:311-314
, 百拇医药 20 郭冬丽, 宁佩芳, 王兰, 袁媛. 胃癌及癌前状态MG7表达的动态观察及分析. 中华流行病学杂志 2003;6:494-497
21 Ren J, Chen Z, Juan SJ, Yong XY, Pan BR, Fan DM. Detection ofcirculating gastric carcinoma-associated
antigen MG7-Ag in human sera using anestablished single determinant immuno-polymerase chain reaction
technique. Cancer 2000;88:280-285
22 Hyodo I, Doi T, Endo H, Hosokawa Y, Nishikawa Y, Tanimizu M, JinnoK, Kotani Y. Clinical significance of plasma
, 百拇医药
vascular endothelial growth factor ingastrointestinal cancer. Eur J Cancer 1998;34:2041-2045
23 Yoshikawa T, Tsuburaya A, Kobayashi O, Sairenji M, Motohashi H,Yanoma S, Noguchi Y. Plasma concentrations of
VEGF and bFGF in patients withgastric carcinoma. Cancer Lett 2000;153:7-12
24 Ohta M, Konno H, Tanaka T, Baba M, Kamiya K, Syouji T, Kondoh K,Watanabe M, Terada H, Nakamura S.
, http://www.100md.com
The significance of circulatingvascular endothelial growth factor (VEGF)protein in gastric cancer. Cancer
Lett 2003;192:215-225
25 Nakajima K, Suzuli T, Shimada H, Hayashi H, Takeda A, Ochiai T.Detection of preoperative serum anti-p53 antibodies
in gastric cancer. Tumour Biol 1999;20:147-152
26 Miki K, Morita M, Sasajima M, Hoshina R, Kanda E, Urita Y.Usefulness of gastric cancer screening using the
, http://www.100md.com
serum pepsinogen test method. Am JGastroenterol 2003;98:735-739
27 Yahagi N, Miki K, Ichinose M, Kakei N, Matsushima M, Kido M,Shimizu Y, Ishihama S, Tsukada S, Kurokawa K. A
minute gastric cancer detected by anew screening method using serum pepsinogen I and II. Adv Exp Med
Biol 1995;362:145-148
28 Miki K. Serum pepsinogen I/II ratio test. Nippon Rinsho 2003;61:92-95
, http://www.100md.com
29 Urita Y, Hike K, Torii N, Kikuchi Y, Kanda E, Sasajima M, Miki K.Serum pepsinogens as a predicator of the topography
of intestinal metaplasia in patientswith atrophic gastritis. Dig Dis Sci 2004;49:795-801
30 孙丽萍, 宫月华, 袁媛. 血清胃蛋白酶原含量作为幽门螺杆菌除菌疗效判定指标的研究. 世界华人消化杂志 2004;12:
1827-1832
31 赵明, 季晓鹏, 郑永胜. 血清胃泌素对胃溃疡及胃癌的诊断价值. 放射免疫学杂志 2003;16:369-374
, 百拇医药
32 Soran A, Aslar AK, Col C. Are preoperative serum gastrin levelsrelated to resectability and survival in gastric cancer?
Int J Clin Pract 2000;54:652-653
33 Triantafillidis JK, Merikas E, Govosdis V, Konstandellou E,Cheracakis P, Barbatzas C, Tzourmakliotis D, Peros G.
Increased fasting serum levels ofgrowth hormone and gastrin in patients with gastric and large bowel
cancer. Hepatogastroenterology 2003;50(Suppl 2):cclvi-cclx
编辑 王谨晖 审读 张海宁, 百拇医药( 白雪蕾,袁 媛)
