胃蛋白酶原及胸苷激酶1对胃癌早期诊断的意义
|
摘要
目的：本研究通过分析血清胃蛋白酶原(PG)Ⅰ、Ⅱ及血清胸苷激酶1(TK1)在胃癌前疾病及胃癌中的表达情况,探讨二者在胃癌早期诊断中的价值,为胃癌早期诊断提供线索。
方法：选取2008年12月～2011年2月来天津港口医院就诊的79例各种胃部疾病患者,均经胃镜检查和(或)手术切除标本的病理组织细胞学诊断。其中胃癌32例(男21例,女11例,平均年龄50.9±5.4岁)；胃溃疡15例(男9例,女6例,平均年龄46.6±4.7岁)；慢性萎缩性胃炎20例(男13例,女7例,平均年龄40.5岁±6.2)；慢性浅表性胃炎12例(男7例,女5例,平均年龄50.2±5.8岁)；健康对照48例(男25例,女23例,平均年龄45±7.3岁),均来自天津港口医院健康查体人群,无消化道、肝脏、肾脏疾病及胃痛病史。分别检测各组PGⅠ、PGⅡ、PGⅠ/PGⅡ比值及TK1、CEA、CA19-9水平。
结果：(1)血清胃蛋白酶原(PG)水平：慢性浅表性胃炎组血清PGⅠ、PGⅡ、PGⅠ/PGⅡ和健康对照组比较均无显著性差异(P>0.05)；慢性萎缩性胃炎组、胃癌组PG1、PGⅠ/PGⅡ均显著低于健康对照组(p<0.01),但PGⅡ无显著性差异(P>0.05)；胃溃疡组与健康对照组相比,血清PGⅠ升高(P<0.05), PGⅡ明显升高(P<0.01),但PGⅠ/PGⅡ无显著性差异(P>0.05)；血清PGI在慢性萎缩性胃炎组和胃癌组间无显著性差异(P>0.05),都与慢性浅表性胃炎组、胃溃疡组之间有极显著性差异(p<0.01),同时,慢性浅表性胃炎组和胃溃疡组之间也存在显著性差异(P<0.05)；血清PGⅡ在慢性萎缩性胃炎组、胃癌组、慢性浅表性胃炎组之间无显著性差异(P>0.05),都与胃溃疡组有极显著性差异(P<0.01); PGⅠ/PGⅡ在慢性浅表性胃炎组、胃溃疡组之间无显著性差异(P>0.05),都与慢性萎缩性胃炎组、胃癌组有极显著性差异(p<0.01)。(2)血清肿瘤标志物癌胚抗原(CEA)、糖类抗原(CA19-9)水平：胃癌组CEA、CA19-9含量明显升高,与健康对照组相比差异有显著性(P<0.05)；而其他良性胃病组中这两者含量与健康对照组相比无显著性差异(P>0.05)。血清CEA、CA19-9在胃癌组与其他胃病组间有显著性差异(p<0.05),而其他各良性胃病组间无显著性差异>0.05)。(3)血清胸苷激酶1(TK1)水平：各实验组间血清TK1浓度有显著性差异(P<0.01)；胃癌组TK1浓度显著高于对照组及胃良性疾病组(P<0.01),胃良性疾病组同对照组相比无显著性差异(P>0.05)；胃癌组中,未治疗组及疗效不显著组TKl浓度显著高于疗效显著组(p<0.01)。
结论：本研究发现,血清胃蛋白酶原及其亚群在胃炎演变到胃癌的过程中,其水平也发生相应的变化。因此,我们可以对胃粘膜状态和不同胃部疾病包括胃癌的风险进行评估,从有效识别胃癌的癌前病变,提高胃癌的早期诊断率。血清胸苷激酶TK1能监测体内细胞的异常增殖,其水平在胃部良、恶性疾病之间存在差异,因而,有助于我们能及时发现癌前病变,极早预测发生胃癌风险和评估发展进程。同时,TK1在胃癌治疗前后水平的变化,能帮助我们了解各治疗方案抑制肿瘤细胞生长的情况,更早评估治疗效果。
Objective: Though analyzing the dynamic expression of serum pepsinogen (PG)Ⅰ,Ⅱand serum thymidine kinase 1 (TK1) in gastric cancer and gastric diseases, to explo-re both value in the early diagnosis of gastric cancer, and to provide clues to early di-agnosis in gastric cancer.
Methods:Choosing79 patients with various gastric diseases from the Tianjin port hospital in February 2009～May 2010.These patiens were confirmed by gastroscopy and (or) surgical pathology specimens cytology. Of which gastric cancer in32cases,21 males and 11 females, average age 50.9 years; gastric ulcer in 15 cases,9 males and 6 females, average age 46.6 years; chronic atrophic gastritis in 20 cases,13 males and 7 females, average age of 40.5 years; 12cases of chronic superficial gastritis;7males and 5females, average age 50.2 years; healthy controls in48cases,25males and 23 females , average age 45 years old, had no digestive tract, liver, kidney disease and stomach p-ain history. Detected PGⅠ, PGⅡ, PGⅠ/PGⅡratio and TK1, CEA, CA19-9 level in each group.
Results:(1) serum pepsinogen (PG) levels:PGⅠ, PGⅡ, PGⅠ/PGⅡbetween chronic superficial gastritis group and the healthy control group showed no significant differe-nce(P<0.05); PGIand PGⅠ/PGⅡin chronic atrophic gastritis group and gastric cancer were significantly lower than the healthy control group (P<0.01), while PGⅡwas no significant difference (P> 0.05); PGI increased slightly (P<0.05) and PGII was signi-ficantly higher (P<0.01) in gastric ulcer group, while PGI/PGII was no difference(P > 0.05). Serum PGI between chronic atrophic gastritis and gastric cancer were no si-gnificant differences (P>0.05), but there were significant difference among gastric ca-ncer, superficial gastritis and gastric ulcer group (P<0.01); serum PGⅡamong atrop-hic gastritis group, gastric cancer group, and superficial gastritis group were no sig-nificant difference (P>0.05), they associated with gastric ulcer group had significant difference (P<0.01); PGI/PGII in superficial gastritis group and gastric ulcers group no significant difference (P>0.05), they associated with gastric cancer and atrophic gastritis had significant difference (P<0.01). (2) Serum tumor markers carcinoembr- Yonic antigen (CEA) and carbohydrate antigen (CA19-9) levels:CEA and CA19-9 in gastric cancer group were significantly increased, compared with the control group th-ere were significant difference (P<0.05); and other groups in both content and health control group showed no significant difference (P>0.05).Serum CEA, CA19-9 betwe-en gastric cancer group and other groups had significant differences (P<0.05), while the other benign gastric diseases were no significant differences (P> 0.05). (3) Serum thymidine kinase 1 (TK1) levels:serumTKl of the experimental group concentrations significant difference (P<0.01); TK1 in gastric cancer group was significantly higher than benign gastric disease group (P<0.01), benign gastric disease group compared wi-th the control group no sigificant difference (P>0.05);TK1 in no treatment group and no significant effect group were significantly higher than the significant effect group (P<0.01).
Conclusion:The serum pepsinogen level dynamically reflects the gastric mucosa state,and it is of great significance in gastric disease identification and early diagnosis of gastric cancer. Thymidine kinase 1 in gastric cancer diagnosis, disease monitoring, prognosis and other aspects of the digestive tract may be superior to other tumor mar-kers, and has better clinical significance.
方法：选取2008年12月～2011年2月来天津港口医院就诊的79例各种胃部疾病患者,均经胃镜检查和(或)手术切除标本的病理组织细胞学诊断。其中胃癌32例(男21例,女11例,平均年龄50.9±5.4岁)；胃溃疡15例(男9例,女6例,平均年龄46.6±4.7岁)；慢性萎缩性胃炎20例(男13例,女7例,平均年龄40.5岁±6.2)；慢性浅表性胃炎12例(男7例,女5例,平均年龄50.2±5.8岁)；健康对照48例(男25例,女23例,平均年龄45±7.3岁),均来自天津港口医院健康查体人群,无消化道、肝脏、肾脏疾病及胃痛病史。分别检测各组PGⅠ、PGⅡ、PGⅠ/PGⅡ比值及TK1、CEA、CA19-9水平。
结果：(1)血清胃蛋白酶原(PG)水平：慢性浅表性胃炎组血清PGⅠ、PGⅡ、PGⅠ/PGⅡ和健康对照组比较均无显著性差异(P>0.05)；慢性萎缩性胃炎组、胃癌组PG1、PGⅠ/PGⅡ均显著低于健康对照组(p<0.01),但PGⅡ无显著性差异(P>0.05)；胃溃疡组与健康对照组相比,血清PGⅠ升高(P<0.05), PGⅡ明显升高(P<0.01),但PGⅠ/PGⅡ无显著性差异(P>0.05)；血清PGI在慢性萎缩性胃炎组和胃癌组间无显著性差异(P>0.05),都与慢性浅表性胃炎组、胃溃疡组之间有极显著性差异(p<0.01),同时,慢性浅表性胃炎组和胃溃疡组之间也存在显著性差异(P<0.05)；血清PGⅡ在慢性萎缩性胃炎组、胃癌组、慢性浅表性胃炎组之间无显著性差异(P>0.05),都与胃溃疡组有极显著性差异(P<0.01); PGⅠ/PGⅡ在慢性浅表性胃炎组、胃溃疡组之间无显著性差异(P>0.05),都与慢性萎缩性胃炎组、胃癌组有极显著性差异(p<0.01)。(2)血清肿瘤标志物癌胚抗原(CEA)、糖类抗原(CA19-9)水平：胃癌组CEA、CA19-9含量明显升高,与健康对照组相比差异有显著性(P<0.05)；而其他良性胃病组中这两者含量与健康对照组相比无显著性差异(P>0.05)。血清CEA、CA19-9在胃癌组与其他胃病组间有显著性差异(p<0.05),而其他各良性胃病组间无显著性差异>0.05)。(3)血清胸苷激酶1(TK1)水平：各实验组间血清TK1浓度有显著性差异(P<0.01)；胃癌组TK1浓度显著高于对照组及胃良性疾病组(P<0.01),胃良性疾病组同对照组相比无显著性差异(P>0.05)；胃癌组中,未治疗组及疗效不显著组TKl浓度显著高于疗效显著组(p<0.01)。
结论：本研究发现,血清胃蛋白酶原及其亚群在胃炎演变到胃癌的过程中,其水平也发生相应的变化。因此,我们可以对胃粘膜状态和不同胃部疾病包括胃癌的风险进行评估,从有效识别胃癌的癌前病变,提高胃癌的早期诊断率。血清胸苷激酶TK1能监测体内细胞的异常增殖,其水平在胃部良、恶性疾病之间存在差异,因而,有助于我们能及时发现癌前病变,极早预测发生胃癌风险和评估发展进程。同时,TK1在胃癌治疗前后水平的变化,能帮助我们了解各治疗方案抑制肿瘤细胞生长的情况,更早评估治疗效果。
Objective: Though analyzing the dynamic expression of serum pepsinogen (PG)Ⅰ,Ⅱand serum thymidine kinase 1 (TK1) in gastric cancer and gastric diseases, to explo-re both value in the early diagnosis of gastric cancer, and to provide clues to early di-agnosis in gastric cancer.
Methods:Choosing79 patients with various gastric diseases from the Tianjin port hospital in February 2009～May 2010.These patiens were confirmed by gastroscopy and (or) surgical pathology specimens cytology. Of which gastric cancer in32cases,21 males and 11 females, average age 50.9 years; gastric ulcer in 15 cases,9 males and 6 females, average age 46.6 years; chronic atrophic gastritis in 20 cases,13 males and 7 females, average age of 40.5 years; 12cases of chronic superficial gastritis;7males and 5females, average age 50.2 years; healthy controls in48cases,25males and 23 females , average age 45 years old, had no digestive tract, liver, kidney disease and stomach p-ain history. Detected PGⅠ, PGⅡ, PGⅠ/PGⅡratio and TK1, CEA, CA19-9 level in each group.
Results:(1) serum pepsinogen (PG) levels:PGⅠ, PGⅡ, PGⅠ/PGⅡbetween chronic superficial gastritis group and the healthy control group showed no significant differe-nce(P<0.05); PGIand PGⅠ/PGⅡin chronic atrophic gastritis group and gastric cancer were significantly lower than the healthy control group (P<0.01), while PGⅡwas no significant difference (P> 0.05); PGI increased slightly (P<0.05) and PGII was signi-ficantly higher (P<0.01) in gastric ulcer group, while PGI/PGII was no difference(P > 0.05). Serum PGI between chronic atrophic gastritis and gastric cancer were no si-gnificant differences (P>0.05), but there were significant difference among gastric ca-ncer, superficial gastritis and gastric ulcer group (P<0.01); serum PGⅡamong atrop-hic gastritis group, gastric cancer group, and superficial gastritis group were no sig-nificant difference (P>0.05), they associated with gastric ulcer group had significant difference (P<0.01); PGI/PGII in superficial gastritis group and gastric ulcers group no significant difference (P>0.05), they associated with gastric cancer and atrophic gastritis had significant difference (P<0.01). (2) Serum tumor markers carcinoembr- Yonic antigen (CEA) and carbohydrate antigen (CA19-9) levels:CEA and CA19-9 in gastric cancer group were significantly increased, compared with the control group th-ere were significant difference (P<0.05); and other groups in both content and health control group showed no significant difference (P>0.05).Serum CEA, CA19-9 betwe-en gastric cancer group and other groups had significant differences (P<0.05), while the other benign gastric diseases were no significant differences (P> 0.05). (3) Serum thymidine kinase 1 (TK1) levels:serumTKl of the experimental group concentrations significant difference (P<0.01); TK1 in gastric cancer group was significantly higher than benign gastric disease group (P<0.01), benign gastric disease group compared wi-th the control group no sigificant difference (P>0.05);TK1 in no treatment group and no significant effect group were significantly higher than the significant effect group (P<0.01).
Conclusion:The serum pepsinogen level dynamically reflects the gastric mucosa state,and it is of great significance in gastric disease identification and early diagnosis of gastric cancer. Thymidine kinase 1 in gastric cancer diagnosis, disease monitoring, prognosis and other aspects of the digestive tract may be superior to other tumor mar-kers, and has better clinical significance.
引文
[1]杨利剑,欧阳静萍,王红玲,等.幽门螺杆菌相关性胃疾病血清PG测定及意义[J].数理医院药学杂志,2006,18(1)：15-17.
[2]钱丽佳.胃蛋白酶原在胃良恶性病变鉴别中的应用[J].南通大学学报(医学版),2010,30(3)：224-228.
[3]Oishi Y, Kiyohara Y, Kubo M,, et al. The serum pepsinogen test as a predictor of gastric cancer:the Hisayama study [J]. Am J Epidemiol,2006,163(7):629.
[4]张毅敏,单绿虎,徐笑红.细胞质胸苷激酶1在106例肿瘤病人的表达[J].中国肿瘤,2008,17(3)：247-248.
[5]管燕,郭其森,山凤莲,等.小细胞肺癌组织胸苷激酶表达临床意义的研究[J].中华肿瘤防治杂志,2010,17(10)：746-748.
[6]张艺,张珏,等.胃蛋白酶原与胰蛋白酶原-2联合检测筛查胃癌的意义[J].中国临床医学,2009,16(2)：548.
[7]周红凤,刘丹,吴瑾,等.胃蛋白酶原和胃癌相关抗原与胃癌的研究进展[J].世界华人消化杂志,2007,15(17)：1940-1946.
[8]刘丹MG-7与胃癌关系的研究现状与进展[J].实用肿瘤学杂志,2006,20(6)：558-560.
[9]郭林,卢仁泉.胃癌患者血清胸苷激酶检测的临床意义[J].检验医学,200823(3)：271-273.
[10]曾雪萍,翟伟.CEA、CA19-9、CA724在胃癌中的表达及临床意义[J].中国实用内科杂志,2006,26(2)：106-108.
[11]王怀志,吴金升,赖大年.胃癌及大肠癌标志物联合测定[J].河南医科大学学报,2008,33(3)：134-135.
[12]Sipponen P, Harkonen M, Alanko A, et al. Diagnosis of atrophic gastritis from a serum sample [J]. J Minerva Gastroenterol Dietol,2007,49(1):11-21.
[13]华嘉临,张艺,黄飚.血清胃蛋白酶原检测诊断消化性溃疡的临床价值[J].山东医药,2010,50(37)：16-17.
[14]张祥宏,朴玉华,王俊灵.血清胃蛋白酶原异常居民胃黏膜变化的随访观察[J].中国肿瘤临床,2008,27(7)：491-494.
[15]朱岚.黄飚,张珏,等.不同人群胃蛋白酶原水平检测分析[J].中国公共卫生,2009,25(10)：1216-1217.
[16]Fumta T.血清胃蛋白酶原的百分率变化是幽门螺杆菌根除的有用标志[J].国外医学消化系疾病分册.2006,18(2)：111.
[17]Pomytkin a TE.The serum content of gastrin-17 and pepsinogenl in patients wi-th duodenalul cerative disease in occupational contactw ithn itrogenous compounds [J]. Klin Lab Diagn,2009,11(11):16-19.
[18]陶梅,张玲霞,张沥,等.血清胃蛋白酶原水平测定在胃疾病中的作用[J].齐齐哈尔医学院学报,2010,31(15)：2353-2355.
[19]李红涛,吴歼春,李彩宁,等.血清胃蛋白酶原诊断胃体黏膜萎缩的研究[J]中华内科杂志,2007,42(10)：141-142.
[20]张祥宏,王俊灵,严霞,等.赞皇县胃癌筛查方法研究简介[J].中国肿瘤杂志,2006,11(7)：384.
[21]Dinis Ribeiro M, Yamaki G, Kmiki K, et al. Meta& analysis on the validity of pepsinogen test for gastric carcinoma, dysplasia or chronic atrophicgastrit is screeni-ng[J]. J Med Semen,2008,11(3):141.
[22]宁慧芳,孙丽萍,刘慧杰,等.胃蛋白酶原C在胃癌及胃癌前疾病诊断中的意义[J].中华医学杂志,2008,84(10)：818-821.
[23]程兆明,李龙,李琳娜. 血清胃蛋白酶原与胃泌素联合检测对胃癌的诊断[J].中华消化内镜杂志,2008,19(1)：32-34.
[24]Nardone G, Rocco A, Staibano S, et al. Diagnostic accuracy of the serum profile of gastric mucosa in relation to histological andmorphometric diagnosis of atrophy [J] . Aliment Pharmacol Ther,2006,22(11):1139.
[25]Iijima K, Abe Y, Kikuchi R, et al. Serum biomarker tests are useful in delineat-ing betweenpatients with gastric atrophy and normal, healthy stomach[J]. World Jo-urnal of Gastroenterology,2009,15(7):853.
[26]赵洪林,刘彤.胃蛋白酶原检测在胃癌诊治中的应用进展[J].山东医药,2008,48(3)：112.
[27]Oishi Y, Kiyohara Y, Kubo M, et al. The serum pepsinogen test as a predictor of gastric cancer:the Hisayama study[J]. Am J Epidemiol,2006,163(7):629.
[28]Watabe H, Mitsushima T, Yamaji Y, et al. Predicting the development of gastric cancer from combining Helicobact erpylori antibodies and serum pepsinogen status:a prospective endoscopic cohort study B [J]. Gut,2006,54(6):764.
[29]Kokkola A, Louhimo J, Puakkainen P, et al. Hel icobacter pylori infect ion and low serum pepsinogen I level as risk factors for gastric carcinoma[J]. World J Gastroenterol,2007,11(7):1032.
[30]Miki K, Fujishiro M, Kodashima S, et al. Long term results of gastric cancer screening using the serum pepsinogen test method among an asymptomatic middle ag-ed Japanese populat ion [J]. Original Article,2009,21(5):78-81.
[31]乌日丽其,许秀举,李艳华,等.蒙古族及汉族胃癌患者血清胃蛋白酶原水平的研究[J].内蒙古医学杂志,2010,42(5)：530-532.
[32]曹勤,冉志华,萧树东.血清胃蛋白酶原、胃泌素-17和幽门螺杆菌IgG抗体筛查萎缩性胃炎和胃癌[J].胃肠病学,2006,11(7)：388-394.
[33]Zhang J, Jia Q, Zou S, et al.Thymidine kinase 1:a proliferation marker for d-etermining prognosis and monitoring the surgical out-come of primary bladder carci-noma patients [J]. Oncol Rep,2006,15(2):455-461.
[34]Wu CJ, Yang RJ, Zhou J, et al. Production and characterisation of a novel Chicken IgY antibody raised against C-terminal pep tide from human thymidine kin-ase 1 [J]. ImmunolMethods,2008,27(7):157-159.
[35]Zhang F, L i H, Pendleton AR, et al. Thymidine kinase 1 immunoassay:a poten-tial marker for breast cancer[J]. CancerDetect Prev,2007,25(1):8-15.
[36]He Q, Zou L, Zhang PA, et al. The clinical significance of thymidine kinase 1 measurement in serum of breast cancer patients using anti-TKl antibody [J]. Int J Biol Markers,2008,15(2):139-146.
[37]He Q, Zou L, Zhang PA, et al. Concentration of thymidine kinase 1 in serum (S-TK1) is amore sensitive p roliferation marker in human solid tumors than its activ-ity[J]. Oncol Rep,2007,14(4):1013.
[38]Zou L, Zhang PG, Zou S, et al. The half-life of thymidine kinase 1 in serum measured by ECL dot blot:a potentialmarker formonitoring the response to surgery of patients with gastric cancer [J]. Int J Biol Markers,2008,17(4):135-140.
[39]Li HX, Zhang S, Lei DS, et al. Serum thymidine kinase 1 is a p rognostic and monitoring factor in patientswith non-small cell lung cancer [J]. Oncol Rep,2006, 13(1):145-149.
[40]Zhang J, JiaQ, Zou S, et a. Thymidine kinase 1:a proliferation marker for determining prognosis and monitoring the surgical outcome of primary bladder carcin-oma patients[J]. Oncol Rep,2006,15(2):455-461.
[41]Chen ZH, Zhou H, Li SL, et al. Serological thymidine kinase 1 indicates an elevated risk for the development of malignant tumors [J]. Anticancer Research, 2008,28(2):3897-3908.
[42]Ke PY, Chang ZF. Mitotic degradation of human thymidine kinase 1 is depend-ent on the anaphase-p romoting comp lex/ cyclosome-CDHl-mediated pathway [J] Mol Cell Biol 2008,24(4):525-526.
[43]Pena DS, Lichter J, Trani M, et al. Quaternary structure change as a mechanism for the regulation of thymidine kinase 1-likenzymes [J]. Structure,2007,15(12):1555-1566.
[44]PoYuan Ke, ChunMei Hu, YiChang Chang, et al. Hiding human thymidine kinase 1 from APC/C-mediated destruction by thymidine binding [J]. FASEB,2007, 21(4):1276-1284.
[45]李艳,张平安,邹力,等.免疫印迹法测定乳腺肿瘤患者胸苷激酶[J].中华检验医学杂志,2008,23(6)：124.
[46]吴建平,毛军,阎玉虎,等.结直肠癌TK1、PCNA表达的研究[J].肿瘤防治研究,2008,27(5)：15-18.
[47]Li HX, Lei DS, Wang XQ, et al. Serum thymidine kinase 1 is a prognostic and monitoring factor in patients with non-small cell lung cancer [J]. Oncol Rep,2006, 13(1):145-149.
[48]Mizutani Y, Nakanishi H, Li YN, et al. Prognostic significance of thymidine kinase activity in renal cell carcinoma[J]. Proc Amer Assoc Cancer Res,2007,45 (3):267.
[49]Brockenbrough S, Rasey J, Grierson J, et al. Assay of cytosolic thymidine kinasel (TK1) activity in human lung lesions[J]. J Nucl Med,2007,48(2):81.
[50]Barthel H, Perumal M, Latigo J, et al. The uptake of 3'-deoxy-3'-[18F] fluor-othymidine into L5178Y tumours in vivois dependent on thymidine kinase 1 protein levels [J].Eur J Nucl Med Mol Imaging,2006,32(3):257-263.
[51]Buck AK, Bommer M, Stilgenbauer S, et al. Molecular imaging of proliferation in malignant lymphoma[J]. Cancer Res,2006,66(22):11055-11061.
[52]Broe BP, Romain S, Daver A, et al. Thymidine Kinase as a proliferative marker: clinical relevance in 1692 primary breast cancer patients[J]. Clin Onco,2009,19(11): 2778-2787.
[53]Gilles SI, Romain S, Casellas P, et al. Mutation analysis in the coding sequence of thymidine kinase 1 in breast and colorectal cancer[J]. Int J BiolMarkers,2008,18 (1):4-6.
[54]WangN, He Q, Skog S, et al. Investigation on cell p roliferation with a new antibody against thymidine kinase 1 [J]. Anal Cell Pathol,2006,23(1):11-19.
[55]He Q, Mao Y, WuJ, et al. Cytosolic thymidine kinase is a specific histopath-ologic tumourmarker for breast carcinomas [J]. Int J Oncol,2007,25 (4):945-953.
[1]钱丽佳.胃蛋白酶原在胃良恶性病变鉴别中的应用[J].南通大学学报(医学版),2010,30(3)：224-228.
[2]Sasazuki S, Inoue M, Iwasaki M, et al. Effect of Helicobacter pylori infection combined with CagA and pepsinogen status on gastric cancer development among Ja-panese men and women:a nested case-control study [J]. Cancer Epidemiol Biomark-ers Prev,2006,15(7):1341-1347.
[3]Oishi Y, Kiyohara Y, Kubo M, et al. The serum pepsinogen test as a predictor of gastric cancer:the Hisayama study [J]. Am J Epidemiol,2006,163(7):629-637.
[4]胡仁静,严子禾,沈洪远,等.血清胃蛋白酶原在胃癌诊断中的价值[J].中国实验诊断学,2010,14(10)：1650-1651.
[5]蒋孟军,肖志坚,张荣军,等.血清胃蛋白酶原Ⅰ、Ⅱ与胃泌素联合检测对胃癌诊断的临床意义[J].标记免疫分析与临床,2008,11(3)：131-133.
[6]Kalinovskii VP, Gamaiunova VB, Shumakov AP, et al. Radioimmunoassay of serum pepsinogen I in chronic gastritis and stomach cancer [J]. Vopr Onkol,2006 ,46(2):153-155.
[7]吕国强,肖志坚,沈安东,等.胃蛋白酶原亚群在胃癌及其术后血清含量变化的临床价值[J].中华消化杂志,2007,19(4)：265-266.
[8]Miki K, Morita M, Sasaima M, et al. Usefulness of gastric cancer screening using the serum pepsinogen test method [J]. Am J Gastroenteml,2008,98(4):735-739.
[9]Mukoubayashi C, Yanaoka K, Ohata H, et al. Serum pepsinogen and gastric cancer screening [J]. Intern Med,2007,46(6):261-266.
[10]Rollan A, Ferreccio C, Gederlini A, et al. Non-invasive diagnosis of gastric mucosal atrophy in an asymptomatic population with high prevalence of gastric canc-er [J]. World J Gastroenterol,2006,12(44):7172-7178.
[11]Kitahara F, Kobayashi K, Sato T, et al. Accuracy of screening tor gastric cancer using serum pepslnogen concentrations [J]. Gut,2006,44(5):693-697.
[12]张祥宏,卜玉华.血清胃蛋白酶原异常居民胃黏膜变化的随访观察[J].中国肿瘤临床,2006,27(7)：491-494.
[13]于中麟,冀明,杨迅,等.血清胃蛋白酶原对胃癌普查的价值探讨[J].中华消化内镜杂志,2008,25(10)：512-515.
[14]Yamaguchi T, Takahashi T, Yokota T, et al. Urinary pepsinogen I as a tumor marker of stomach cancer after total gastrectomy [J]. Cancer,2005,68(4):906-909.
[15]肖志坚,蒋孟军,肖华龙,等.胃癌患者全胃切除后血清PG、PGII含量变化与胃癌复发的关系[J].癌症,2006,19(1)：66-68.
[16]袁荣华,孙永强,翟晓峰,等. 胃癌手术治疗前后血清胃蛋白酶原含量分析[J].交通医学,2009,23(2)：139-140.
[17]Fema ndez R, Vizoso F, Rodrfguez JC, et al. Expression and prognostie signifi-cance of pepsinogen C in gastric carcinoma [J]. Annals Surg Oneol,2006,7(7):5 08-514.
[18]Wong BC, Lam SK, Wong WM, et al. Helicobacter pylon eradication to prevent gastric cancer in a high-risk region of China:a randomized controlled trial [J]. AMM ,2007,291(2):187-194.
[19]Lu XL, Qian KD, Tang xq, et al. Distribution of H pylori antigens in gastric mucosa and its significance [J]. Zhejiang Univ Sci,2008,5(2):242-245.
[20]Sipponen P, Harkonen M, Alanko A, et al. Diagnosis of atrophic gastritis from a serum sample [J]. Minerva Gastroenterd Dietal,2008,40(1):11-21.
[21]Martin W, Urszula K, Nils-Egil M, et al. Structures of thymidine kinase 1 of human and mycoplasmic origin [J].PNAS,2007,101(52):17970-17975.
[22]Topolcan O, Holubec L. The role of thymidine kinase 1 in cancer disease [J]. E-xpert Opin Med Diagn,2008,14(2):129-141.
[23]张勇超.结直肠癌患者血清胸苷激酶的检测及临床价值[J].医药论坛杂志,2-009,30(7)：28-30.
[24]郭林,卢仁泉.胃癌患者血清胸苷激酶检测的临床意义[J].检验医学,2008,23(3)：271-273.
[25]吴建平,毛军,阎玉虎,等.结直肠癌TK1、PCNA表达的研究[J].肿瘤防治研究,2006,27(5)：15-18.
[26]Topolcan O, Holuber LJ, Finek J, et al. Changes of thymidine kinase (TK) during adjuvant and palliative chemotherapy[J]. Anticancer Res,2006,25(3):18 31-1833.
[27]Zhang J, Jia Q, Zou S, et al. Thymidine kinase 1:a proliferation marker for determining prognosis and monitoring the surgical outcome of primary bladder carcin-oma patients [J]. Oncol Rep,2006,15(2):455-461.
[28]Li HX, Zhang S, Lei DS, et al. Serum thymidine kinase 1 is a prognostic and monitoring factor in patients with nonsmall cell lung cancer [J]. Oncology Report, 2008,13(1):145-149.
[29]He Q, Fornander T, Johansson H, et al. Thymidine kinase 1 in serum predicts increased risk of distant or loco-regional recurrence following surgery in patients with early breastcancer [J]. Anticancer Res,2008,26(6):4753-4759.
[30]O'Neill KL, Zhang F, Li H, et al. Thymidine kinase 1-a prognostic and diagno-stic indicator in ALL and AML patients [J]. Leukemia,2007,21(3):560-563.
[2]钱丽佳.胃蛋白酶原在胃良恶性病变鉴别中的应用[J].南通大学学报(医学版),2010,30(3)：224-228.
[3]Oishi Y, Kiyohara Y, Kubo M,, et al. The serum pepsinogen test as a predictor of gastric cancer:the Hisayama study [J]. Am J Epidemiol,2006,163(7):629.
[4]张毅敏,单绿虎,徐笑红.细胞质胸苷激酶1在106例肿瘤病人的表达[J].中国肿瘤,2008,17(3)：247-248.
[5]管燕,郭其森,山凤莲,等.小细胞肺癌组织胸苷激酶表达临床意义的研究[J].中华肿瘤防治杂志,2010,17(10)：746-748.
[6]张艺,张珏,等.胃蛋白酶原与胰蛋白酶原-2联合检测筛查胃癌的意义[J].中国临床医学,2009,16(2)：548.
[7]周红凤,刘丹,吴瑾,等.胃蛋白酶原和胃癌相关抗原与胃癌的研究进展[J].世界华人消化杂志,2007,15(17)：1940-1946.
[8]刘丹MG-7与胃癌关系的研究现状与进展[J].实用肿瘤学杂志,2006,20(6)：558-560.
[9]郭林,卢仁泉.胃癌患者血清胸苷激酶检测的临床意义[J].检验医学,200823(3)：271-273.
[10]曾雪萍,翟伟.CEA、CA19-9、CA724在胃癌中的表达及临床意义[J].中国实用内科杂志,2006,26(2)：106-108.
[11]王怀志,吴金升,赖大年.胃癌及大肠癌标志物联合测定[J].河南医科大学学报,2008,33(3)：134-135.
[12]Sipponen P, Harkonen M, Alanko A, et al. Diagnosis of atrophic gastritis from a serum sample [J]. J Minerva Gastroenterol Dietol,2007,49(1):11-21.
[13]华嘉临,张艺,黄飚.血清胃蛋白酶原检测诊断消化性溃疡的临床价值[J].山东医药,2010,50(37)：16-17.
[14]张祥宏,朴玉华,王俊灵.血清胃蛋白酶原异常居民胃黏膜变化的随访观察[J].中国肿瘤临床,2008,27(7)：491-494.
[15]朱岚.黄飚,张珏,等.不同人群胃蛋白酶原水平检测分析[J].中国公共卫生,2009,25(10)：1216-1217.
[16]Fumta T.血清胃蛋白酶原的百分率变化是幽门螺杆菌根除的有用标志[J].国外医学消化系疾病分册.2006,18(2)：111.
[17]Pomytkin a TE.The serum content of gastrin-17 and pepsinogenl in patients wi-th duodenalul cerative disease in occupational contactw ithn itrogenous compounds [J]. Klin Lab Diagn,2009,11(11):16-19.
[18]陶梅,张玲霞,张沥,等.血清胃蛋白酶原水平测定在胃疾病中的作用[J].齐齐哈尔医学院学报,2010,31(15)：2353-2355.
[19]李红涛,吴歼春,李彩宁,等.血清胃蛋白酶原诊断胃体黏膜萎缩的研究[J]中华内科杂志,2007,42(10)：141-142.
[20]张祥宏,王俊灵,严霞,等.赞皇县胃癌筛查方法研究简介[J].中国肿瘤杂志,2006,11(7)：384.
[21]Dinis Ribeiro M, Yamaki G, Kmiki K, et al. Meta& analysis on the validity of pepsinogen test for gastric carcinoma, dysplasia or chronic atrophicgastrit is screeni-ng[J]. J Med Semen,2008,11(3):141.
[22]宁慧芳,孙丽萍,刘慧杰,等.胃蛋白酶原C在胃癌及胃癌前疾病诊断中的意义[J].中华医学杂志,2008,84(10)：818-821.
[23]程兆明,李龙,李琳娜. 血清胃蛋白酶原与胃泌素联合检测对胃癌的诊断[J].中华消化内镜杂志,2008,19(1)：32-34.
[24]Nardone G, Rocco A, Staibano S, et al. Diagnostic accuracy of the serum profile of gastric mucosa in relation to histological andmorphometric diagnosis of atrophy [J] . Aliment Pharmacol Ther,2006,22(11):1139.
[25]Iijima K, Abe Y, Kikuchi R, et al. Serum biomarker tests are useful in delineat-ing betweenpatients with gastric atrophy and normal, healthy stomach[J]. World Jo-urnal of Gastroenterology,2009,15(7):853.
[26]赵洪林,刘彤.胃蛋白酶原检测在胃癌诊治中的应用进展[J].山东医药,2008,48(3)：112.
[27]Oishi Y, Kiyohara Y, Kubo M, et al. The serum pepsinogen test as a predictor of gastric cancer:the Hisayama study[J]. Am J Epidemiol,2006,163(7):629.
[28]Watabe H, Mitsushima T, Yamaji Y, et al. Predicting the development of gastric cancer from combining Helicobact erpylori antibodies and serum pepsinogen status:a prospective endoscopic cohort study B [J]. Gut,2006,54(6):764.
[29]Kokkola A, Louhimo J, Puakkainen P, et al. Hel icobacter pylori infect ion and low serum pepsinogen I level as risk factors for gastric carcinoma[J]. World J Gastroenterol,2007,11(7):1032.
[30]Miki K, Fujishiro M, Kodashima S, et al. Long term results of gastric cancer screening using the serum pepsinogen test method among an asymptomatic middle ag-ed Japanese populat ion [J]. Original Article,2009,21(5):78-81.
[31]乌日丽其,许秀举,李艳华,等.蒙古族及汉族胃癌患者血清胃蛋白酶原水平的研究[J].内蒙古医学杂志,2010,42(5)：530-532.
[32]曹勤,冉志华,萧树东.血清胃蛋白酶原、胃泌素-17和幽门螺杆菌IgG抗体筛查萎缩性胃炎和胃癌[J].胃肠病学,2006,11(7)：388-394.
[33]Zhang J, Jia Q, Zou S, et al.Thymidine kinase 1:a proliferation marker for d-etermining prognosis and monitoring the surgical out-come of primary bladder carci-noma patients [J]. Oncol Rep,2006,15(2):455-461.
[34]Wu CJ, Yang RJ, Zhou J, et al. Production and characterisation of a novel Chicken IgY antibody raised against C-terminal pep tide from human thymidine kin-ase 1 [J]. ImmunolMethods,2008,27(7):157-159.
[35]Zhang F, L i H, Pendleton AR, et al. Thymidine kinase 1 immunoassay:a poten-tial marker for breast cancer[J]. CancerDetect Prev,2007,25(1):8-15.
[36]He Q, Zou L, Zhang PA, et al. The clinical significance of thymidine kinase 1 measurement in serum of breast cancer patients using anti-TKl antibody [J]. Int J Biol Markers,2008,15(2):139-146.
[37]He Q, Zou L, Zhang PA, et al. Concentration of thymidine kinase 1 in serum (S-TK1) is amore sensitive p roliferation marker in human solid tumors than its activ-ity[J]. Oncol Rep,2007,14(4):1013.
[38]Zou L, Zhang PG, Zou S, et al. The half-life of thymidine kinase 1 in serum measured by ECL dot blot:a potentialmarker formonitoring the response to surgery of patients with gastric cancer [J]. Int J Biol Markers,2008,17(4):135-140.
[39]Li HX, Zhang S, Lei DS, et al. Serum thymidine kinase 1 is a p rognostic and monitoring factor in patientswith non-small cell lung cancer [J]. Oncol Rep,2006, 13(1):145-149.
[40]Zhang J, JiaQ, Zou S, et a. Thymidine kinase 1:a proliferation marker for determining prognosis and monitoring the surgical outcome of primary bladder carcin-oma patients[J]. Oncol Rep,2006,15(2):455-461.
[41]Chen ZH, Zhou H, Li SL, et al. Serological thymidine kinase 1 indicates an elevated risk for the development of malignant tumors [J]. Anticancer Research, 2008,28(2):3897-3908.
[42]Ke PY, Chang ZF. Mitotic degradation of human thymidine kinase 1 is depend-ent on the anaphase-p romoting comp lex/ cyclosome-CDHl-mediated pathway [J] Mol Cell Biol 2008,24(4):525-526.
[43]Pena DS, Lichter J, Trani M, et al. Quaternary structure change as a mechanism for the regulation of thymidine kinase 1-likenzymes [J]. Structure,2007,15(12):1555-1566.
[44]PoYuan Ke, ChunMei Hu, YiChang Chang, et al. Hiding human thymidine kinase 1 from APC/C-mediated destruction by thymidine binding [J]. FASEB,2007, 21(4):1276-1284.
[45]李艳,张平安,邹力,等.免疫印迹法测定乳腺肿瘤患者胸苷激酶[J].中华检验医学杂志,2008,23(6)：124.
[46]吴建平,毛军,阎玉虎,等.结直肠癌TK1、PCNA表达的研究[J].肿瘤防治研究,2008,27(5)：15-18.
[47]Li HX, Lei DS, Wang XQ, et al. Serum thymidine kinase 1 is a prognostic and monitoring factor in patients with non-small cell lung cancer [J]. Oncol Rep,2006, 13(1):145-149.
[48]Mizutani Y, Nakanishi H, Li YN, et al. Prognostic significance of thymidine kinase activity in renal cell carcinoma[J]. Proc Amer Assoc Cancer Res,2007,45 (3):267.
[49]Brockenbrough S, Rasey J, Grierson J, et al. Assay of cytosolic thymidine kinasel (TK1) activity in human lung lesions[J]. J Nucl Med,2007,48(2):81.
[50]Barthel H, Perumal M, Latigo J, et al. The uptake of 3'-deoxy-3'-[18F] fluor-othymidine into L5178Y tumours in vivois dependent on thymidine kinase 1 protein levels [J].Eur J Nucl Med Mol Imaging,2006,32(3):257-263.
[51]Buck AK, Bommer M, Stilgenbauer S, et al. Molecular imaging of proliferation in malignant lymphoma[J]. Cancer Res,2006,66(22):11055-11061.
[52]Broe BP, Romain S, Daver A, et al. Thymidine Kinase as a proliferative marker: clinical relevance in 1692 primary breast cancer patients[J]. Clin Onco,2009,19(11): 2778-2787.
[53]Gilles SI, Romain S, Casellas P, et al. Mutation analysis in the coding sequence of thymidine kinase 1 in breast and colorectal cancer[J]. Int J BiolMarkers,2008,18 (1):4-6.
[54]WangN, He Q, Skog S, et al. Investigation on cell p roliferation with a new antibody against thymidine kinase 1 [J]. Anal Cell Pathol,2006,23(1):11-19.
[55]He Q, Mao Y, WuJ, et al. Cytosolic thymidine kinase is a specific histopath-ologic tumourmarker for breast carcinomas [J]. Int J Oncol,2007,25 (4):945-953.
[1]钱丽佳.胃蛋白酶原在胃良恶性病变鉴别中的应用[J].南通大学学报(医学版),2010,30(3)：224-228.
[2]Sasazuki S, Inoue M, Iwasaki M, et al. Effect of Helicobacter pylori infection combined with CagA and pepsinogen status on gastric cancer development among Ja-panese men and women:a nested case-control study [J]. Cancer Epidemiol Biomark-ers Prev,2006,15(7):1341-1347.
[3]Oishi Y, Kiyohara Y, Kubo M, et al. The serum pepsinogen test as a predictor of gastric cancer:the Hisayama study [J]. Am J Epidemiol,2006,163(7):629-637.
[4]胡仁静,严子禾,沈洪远,等.血清胃蛋白酶原在胃癌诊断中的价值[J].中国实验诊断学,2010,14(10)：1650-1651.
[5]蒋孟军,肖志坚,张荣军,等.血清胃蛋白酶原Ⅰ、Ⅱ与胃泌素联合检测对胃癌诊断的临床意义[J].标记免疫分析与临床,2008,11(3)：131-133.
[6]Kalinovskii VP, Gamaiunova VB, Shumakov AP, et al. Radioimmunoassay of serum pepsinogen I in chronic gastritis and stomach cancer [J]. Vopr Onkol,2006 ,46(2):153-155.
[7]吕国强,肖志坚,沈安东,等.胃蛋白酶原亚群在胃癌及其术后血清含量变化的临床价值[J].中华消化杂志,2007,19(4)：265-266.
[8]Miki K, Morita M, Sasaima M, et al. Usefulness of gastric cancer screening using the serum pepsinogen test method [J]. Am J Gastroenteml,2008,98(4):735-739.
[9]Mukoubayashi C, Yanaoka K, Ohata H, et al. Serum pepsinogen and gastric cancer screening [J]. Intern Med,2007,46(6):261-266.
[10]Rollan A, Ferreccio C, Gederlini A, et al. Non-invasive diagnosis of gastric mucosal atrophy in an asymptomatic population with high prevalence of gastric canc-er [J]. World J Gastroenterol,2006,12(44):7172-7178.
[11]Kitahara F, Kobayashi K, Sato T, et al. Accuracy of screening tor gastric cancer using serum pepslnogen concentrations [J]. Gut,2006,44(5):693-697.
[12]张祥宏,卜玉华.血清胃蛋白酶原异常居民胃黏膜变化的随访观察[J].中国肿瘤临床,2006,27(7)：491-494.
[13]于中麟,冀明,杨迅,等.血清胃蛋白酶原对胃癌普查的价值探讨[J].中华消化内镜杂志,2008,25(10)：512-515.
[14]Yamaguchi T, Takahashi T, Yokota T, et al. Urinary pepsinogen I as a tumor marker of stomach cancer after total gastrectomy [J]. Cancer,2005,68(4):906-909.
[15]肖志坚,蒋孟军,肖华龙,等.胃癌患者全胃切除后血清PG、PGII含量变化与胃癌复发的关系[J].癌症,2006,19(1)：66-68.
[16]袁荣华,孙永强,翟晓峰,等. 胃癌手术治疗前后血清胃蛋白酶原含量分析[J].交通医学,2009,23(2)：139-140.
[17]Fema ndez R, Vizoso F, Rodrfguez JC, et al. Expression and prognostie signifi-cance of pepsinogen C in gastric carcinoma [J]. Annals Surg Oneol,2006,7(7):5 08-514.
[18]Wong BC, Lam SK, Wong WM, et al. Helicobacter pylon eradication to prevent gastric cancer in a high-risk region of China:a randomized controlled trial [J]. AMM ,2007,291(2):187-194.
[19]Lu XL, Qian KD, Tang xq, et al. Distribution of H pylori antigens in gastric mucosa and its significance [J]. Zhejiang Univ Sci,2008,5(2):242-245.
[20]Sipponen P, Harkonen M, Alanko A, et al. Diagnosis of atrophic gastritis from a serum sample [J]. Minerva Gastroenterd Dietal,2008,40(1):11-21.
[21]Martin W, Urszula K, Nils-Egil M, et al. Structures of thymidine kinase 1 of human and mycoplasmic origin [J].PNAS,2007,101(52):17970-17975.
[22]Topolcan O, Holubec L. The role of thymidine kinase 1 in cancer disease [J]. E-xpert Opin Med Diagn,2008,14(2):129-141.
[23]张勇超.结直肠癌患者血清胸苷激酶的检测及临床价值[J].医药论坛杂志,2-009,30(7)：28-30.
[24]郭林,卢仁泉.胃癌患者血清胸苷激酶检测的临床意义[J].检验医学,2008,23(3)：271-273.
[25]吴建平,毛军,阎玉虎,等.结直肠癌TK1、PCNA表达的研究[J].肿瘤防治研究,2006,27(5)：15-18.
[26]Topolcan O, Holuber LJ, Finek J, et al. Changes of thymidine kinase (TK) during adjuvant and palliative chemotherapy[J]. Anticancer Res,2006,25(3):18 31-1833.
[27]Zhang J, Jia Q, Zou S, et al. Thymidine kinase 1:a proliferation marker for determining prognosis and monitoring the surgical outcome of primary bladder carcin-oma patients [J]. Oncol Rep,2006,15(2):455-461.
[28]Li HX, Zhang S, Lei DS, et al. Serum thymidine kinase 1 is a prognostic and monitoring factor in patients with nonsmall cell lung cancer [J]. Oncology Report, 2008,13(1):145-149.
[29]He Q, Fornander T, Johansson H, et al. Thymidine kinase 1 in serum predicts increased risk of distant or loco-regional recurrence following surgery in patients with early breastcancer [J]. Anticancer Res,2008,26(6):4753-4759.
[30]O'Neill KL, Zhang F, Li H, et al. Thymidine kinase 1-a prognostic and diagno-stic indicator in ALL and AML patients [J]. Leukemia,2007,21(3):560-563.