PGC在不同胃疾病黏膜中表达和血清学水平比较及其与Hp的关系
|
摘要
目的应用免疫组化法(SABC法)检测胃蛋白酶原C(PGC)在单纯浅表性胃炎、单纯萎缩性胃炎、伴肠化、伴异型增生、胃癌各组中的表达情况;同一组病例中Hp(+)病例在根治前后PGC的表达情况;应用ELISA法检测以上各组血清sPGC、sPGA浓度及Hp(+)病例在根治前后血清sPG浓度;分析胃蛋白酶原与幽门螺杆菌的关系;分析PGC表达水平与血清sPGC、sPGA的相关性,给临床工作提供更有益的信息,进一步诠释胃蛋白酶原作为胃癌标志物在诊治中的应用意义。
方法利用延安大学附属医院病理科2008-2009年胃镜及手术活检标本, 49例单纯浅表性胃炎、35例单纯萎缩性胃炎、40例伴肠化、39例伴异型增生、41例腺癌;采用SABC法检测各组胃黏膜PGC表达情况;ELISA法检测血清sPGC、sPGA值,对实验所得结果采用SPSS16.0统计软件包进行统计学处理,计数资料采用χ2检验进行分析,计量资料采用t检验、方差分析;组织表达与血清含量相关性采用Pearson相关性分析;P<0.05有统计学意义。
结果
1. PGC在各种胃疾病黏膜组织中的表达
PGC在不同胃疾病黏膜中的表达有差异(P=0.000):在单纯浅表性胃炎(95.9%)、单纯萎缩性胃炎(77.1%)、伴肠化(55.0%)、伴异型增生(51.3%)、腺癌(7.3%)中PGC阳性率呈现递减。单纯浅表组与其余各组相比阳性率差异有统计学意义(P值均小于0.05);伴肠化与伴异型增生组相比,差异无统计学意义(P=0.741);单纯萎缩与肠化/异型增生、胃癌PGC阳性率比较差异有统计学意义(P值均小于0.05);肠化/异型增生与胃癌PGC阳性率有显著差异(P值均小于0.05)。
2.各种胃疾病患者的PG血清浓度比较
本组实验测得sPGC、sPGA浓度在各组间比较差异有统计学意义(Pa=0.000 Pc=0.000)。sPGA在浅表组与其余各组相比呈现递减,差异有统计学意义(P值均小于0.05) ;萎缩组与其余各组相比差异有统计学意义(P值均小于0.05) ;肠化组与异型增生组相比差异无统计学意义(P=0.264);肠化组/异型增生组与胃癌组比较差异有统计学意义(P值均小于0.05);sPGC从单纯浅表-单纯萎缩-伴肠化/异性增生-胃癌,sPGC浓度也表现为逐渐上降趋势,总体上各组sPGC浓度差异有统计学差异(P<0.05),胃癌组与其他各组相比差异显著(P值均小于0.05),但其余组间相互比较差异无统计学意义(P值均大于0.05)。
3. PGC不同组织表达与血清PG浓度的比较
从浅表-萎缩-肠化-异型增生-胃癌,随粘膜病变程度加深,组织PGC表达与血清sPGA呈负相关、与sPGC呈正相(ra=0.956,Pa= 0.011;rc=-0.968,Pc=0.007)。
4.在Hp(+)组与(-)组的PGC表达情况和sPGC/sPGA血清学比较
PGC表达在Hp(+)组和(-)组间比较差异有统计学意义(P<0.05),在单纯萎缩组、伴肠化组、伴异型增生组PGC表达率在Hp(+)组显著低于Hp(-)组(P值均小于0.05),但在单纯浅表组二者差异无统计学意义(P=1.000)。
在根除成功组不同胃疾病黏膜PGC表达率表现为明显的上升趋势,但在单纯浅表组和单纯萎缩组,差异无统计学意义,而伴肠化组、伴异型增生组则差异显著(各组P值依次为1.000,0.242,0.024,0.030)。根除失败组,PGC表达率未见明显变化,差异无统计学意义,(各组P值分别为0.271,1.000,1.000,1.000)。血清PG值在Hp(+)组和(-)组浓度比较差异显著(P值均小于0.05);sPGA仅在单纯浅表组的Hp(+)组∕Hp(-)组相比有统计学意义(P=0.000),在其余组的Hp(+)组∕Hp(-)组相比无显著意义(P值均大于0.05);sPGC在各组的Hp(+)组∕Hp(-)组相比差异有统计学意义(P值均小于0.05)。
根除成功组血清sPGA、sPGC值在治疗前后比较有统计学意义(P值均小于0.05);根除失败组sPGC、sPGA值在治疗前后相比差异无统计学意义(P值均大于0.05);
结论
1. PGC表达在不同年龄、性别的胃疾病患者中无显著差异;sPGA、sPGC在男性高于女性,65岁以上患者的血清PG值普遍低于65岁以下患者;
2. PGC在不同胃疾病黏膜中的动态表达呈逐渐降低的趋势,提示胃黏膜细胞恶性表达与PGC抗原表达呈负相关,提示这个指标与胃疾病的发生发展有良好的相关性;
3.血清sPGA明显降低则胃癌危险性增高,提示血清PG降低可能与胃癌的发生发展有关;
4.单独应用sPGA或者sPGC进行胃黏膜疾病的检测,临床意义不显著。但若同时进行血清PG值及PGC抗原表达率检测,二具者有良好的相关性,可作为临床筛查胃癌及癌前疾病的指标;
5. Hp阳性伴有PGC阴性表达和低sPGA、高sPGC的患者胃疾病恶性程度高,应密切随访;
6. Hp根治成功后血清PG值显著下降; PGC表达在根治前后的肠化组、异型增生组有显著差异,提示Hp根除可以使PGC表达率增加,或许可以减慢肠化、异型增生这些癌前病变向胃癌的发展速度。
Objective Immunohistochemical method(SABC) was used to detect the expression levels of PGC in CSG,CAG,IM,DYS and GC tissue, variation in the same group before and after radical cure for Hp infection. To detect the level of sPGA, sPGC and the variation in serum pepsinogen concentration before and after Helicobacter pylori eradication by ELISA. To analyze the relationship between the PGC and Hp, the correlation between the expression of PGC and the level of sPGA, sPGC, which will help to guidance the clinical work , also further interpreted PGC may be a good molecular maker for the early diagnosis of gastric carcinoma .
Method The experiment was performed from 2008 to 2009 at the Department of Pathology in Affiliated Hospital of Medical College of Yan’an University . The expression of PGC was detected by immunohistochemistry in 49 chronic superficial gastritis(CSG), 35 chronic atrophic gastritis (CAG), 40intestinal metaplasia(IM), 39 Dysplasia (DYS)and 41gastric cancer (Ca) in 204 endoscopic biopsy specimens. To detect the level of sPGA, sPGC by ELISA. The data were analyzed for significance using the statistical software SPSS 16.0 computer package. Chi-square test was used in the analysis of enumeration data, the differences of measurement data were compared with the analysis of variance and t test, Tissue expression and serum in correlation analysis using Person. P <0.05 statistically significant.
Result
1. PGC Expression among different gastric disease tissue there were differences in PGC Expression among different gastric disease tissue, the expression of pepsinogenC decreased significantly on sequence(P<0.05 ).the positive rate of PGC is 95.9%,77.1%,55.0%,51.3%,7.3% (CSG,CAG, IM,DYS,Ca). The positive rate of PGC in CSG was significantly higher than in the others(P<0.05), The positive rate was significantly higher in CAG than in IM,DYS and Ca, but there is no significant difference between IM and DYS(P>0.05). The positive rate was significantly lower in Ca than in others(P<0.05).
2. Comparison Serum Pepsinogen Levels in patients with different gastric diseases
There were differences in concentration of sPGA, sPGC among the groups. And there was extreme significant statistics difference (P< 0.05). sPGA decreased significantly on sequence(P<0.05). sPGC increased significantly on sequence(P<0.05).sPGC in Ca is higher than in others(P<0.05),but no significant difference in serum PGC were detected in CSG,CAG, IM,DYS(P>0.05).
3. Comparisons between different expression of tissue PGC and concentration of serum PG
By the decrease of PGC expression, lesion tissue in CAG,CSG,IM,DYS,Ca, their concentration of serum PGC was increased and their sPGA concentration was decreased, and there is statistic difference(P<0.05). The sPGA decreased, the sPGC increased along with decrease of PGC expression in lesion tissue, they have good relativity and the statistic difference was similar (ra=0.956,Pa= 0.011;rc=-0.968,Pc=0.007).
4. Comparisons between different expression of tissue PGC and concenrtation of serum PG in H.p infections and non-infections
Rate of PGC expression in groups (CSG,IM,DYS,Ca) of H.p infection was lower than that of non-infection(P<0.05),but there is no statistic difference in CAG(P>0.05). The rate of PGC increased significantly on sequence in different groups of eradication successfully (P<0.05),and in IM,DYS,there is statistic difference(P<0.05), but in CAG or CSG, there is no difference(P>0.05). The difference was not statistically significant in the gruoups of eradication failure (P>0.05).
Concentration of sPGA, sPGC in groups of H.p infection was higher than that of non-infection (P<0.05). There is significantly difference of sPGC among the gruoups (P<0.05).but, only in CAG there is significantly difference of sPGA(P<0.05). Concentration of sPGA, sPGC is lower in different groups of eradication successfully than before (P<0.05), but the difference was not statistically significant in the gruoups of eradication failure (P>0.05).
Conclusion
1. the rate of PGC expression in different age and sex of gastric disease in patients with no significant differences. sPGA and sPGC is higher in male than in female, is higher in <65 guoups than in≥65 groups.
2. Tissue expression of PGC is negative to the malignant degree of gastric mucosa cell and positive with the development of gastric of gastric mucosa diseases.
3. Serum sPGA decreased obviously is an increased risk.
4. The test, which only use sPGA or sPGC to detect gastric mucosa, isn’t a marked in clinic, and at the same time the detection of sPG is relative to the tissue expression of PGC antigen, it is a convenient, economic maker to screen and diagnose gastric mucosa disease, and has some clinical value.
5. the patients with H.p infection ,low sPGA or high sPGC and negative expression of PGC should be closely followed.
6. Concentration of sPGA, sPGC is lower of eradication successfully than before (P<0.05).The rate of PGC increased significantly on sequence of eradication successfully in IM, DYS(P<0.05). It shows Hp perhaps can slow IM, DYS of these premalignant changes to the development of cancer.
方法利用延安大学附属医院病理科2008-2009年胃镜及手术活检标本, 49例单纯浅表性胃炎、35例单纯萎缩性胃炎、40例伴肠化、39例伴异型增生、41例腺癌;采用SABC法检测各组胃黏膜PGC表达情况;ELISA法检测血清sPGC、sPGA值,对实验所得结果采用SPSS16.0统计软件包进行统计学处理,计数资料采用χ2检验进行分析,计量资料采用t检验、方差分析;组织表达与血清含量相关性采用Pearson相关性分析;P<0.05有统计学意义。
结果
1. PGC在各种胃疾病黏膜组织中的表达
PGC在不同胃疾病黏膜中的表达有差异(P=0.000):在单纯浅表性胃炎(95.9%)、单纯萎缩性胃炎(77.1%)、伴肠化(55.0%)、伴异型增生(51.3%)、腺癌(7.3%)中PGC阳性率呈现递减。单纯浅表组与其余各组相比阳性率差异有统计学意义(P值均小于0.05);伴肠化与伴异型增生组相比,差异无统计学意义(P=0.741);单纯萎缩与肠化/异型增生、胃癌PGC阳性率比较差异有统计学意义(P值均小于0.05);肠化/异型增生与胃癌PGC阳性率有显著差异(P值均小于0.05)。
2.各种胃疾病患者的PG血清浓度比较
本组实验测得sPGC、sPGA浓度在各组间比较差异有统计学意义(Pa=0.000 Pc=0.000)。sPGA在浅表组与其余各组相比呈现递减,差异有统计学意义(P值均小于0.05) ;萎缩组与其余各组相比差异有统计学意义(P值均小于0.05) ;肠化组与异型增生组相比差异无统计学意义(P=0.264);肠化组/异型增生组与胃癌组比较差异有统计学意义(P值均小于0.05);sPGC从单纯浅表-单纯萎缩-伴肠化/异性增生-胃癌,sPGC浓度也表现为逐渐上降趋势,总体上各组sPGC浓度差异有统计学差异(P<0.05),胃癌组与其他各组相比差异显著(P值均小于0.05),但其余组间相互比较差异无统计学意义(P值均大于0.05)。
3. PGC不同组织表达与血清PG浓度的比较
从浅表-萎缩-肠化-异型增生-胃癌,随粘膜病变程度加深,组织PGC表达与血清sPGA呈负相关、与sPGC呈正相(ra=0.956,Pa= 0.011;rc=-0.968,Pc=0.007)。
4.在Hp(+)组与(-)组的PGC表达情况和sPGC/sPGA血清学比较
PGC表达在Hp(+)组和(-)组间比较差异有统计学意义(P<0.05),在单纯萎缩组、伴肠化组、伴异型增生组PGC表达率在Hp(+)组显著低于Hp(-)组(P值均小于0.05),但在单纯浅表组二者差异无统计学意义(P=1.000)。
在根除成功组不同胃疾病黏膜PGC表达率表现为明显的上升趋势,但在单纯浅表组和单纯萎缩组,差异无统计学意义,而伴肠化组、伴异型增生组则差异显著(各组P值依次为1.000,0.242,0.024,0.030)。根除失败组,PGC表达率未见明显变化,差异无统计学意义,(各组P值分别为0.271,1.000,1.000,1.000)。血清PG值在Hp(+)组和(-)组浓度比较差异显著(P值均小于0.05);sPGA仅在单纯浅表组的Hp(+)组∕Hp(-)组相比有统计学意义(P=0.000),在其余组的Hp(+)组∕Hp(-)组相比无显著意义(P值均大于0.05);sPGC在各组的Hp(+)组∕Hp(-)组相比差异有统计学意义(P值均小于0.05)。
根除成功组血清sPGA、sPGC值在治疗前后比较有统计学意义(P值均小于0.05);根除失败组sPGC、sPGA值在治疗前后相比差异无统计学意义(P值均大于0.05);
结论
1. PGC表达在不同年龄、性别的胃疾病患者中无显著差异;sPGA、sPGC在男性高于女性,65岁以上患者的血清PG值普遍低于65岁以下患者;
2. PGC在不同胃疾病黏膜中的动态表达呈逐渐降低的趋势,提示胃黏膜细胞恶性表达与PGC抗原表达呈负相关,提示这个指标与胃疾病的发生发展有良好的相关性;
3.血清sPGA明显降低则胃癌危险性增高,提示血清PG降低可能与胃癌的发生发展有关;
4.单独应用sPGA或者sPGC进行胃黏膜疾病的检测,临床意义不显著。但若同时进行血清PG值及PGC抗原表达率检测,二具者有良好的相关性,可作为临床筛查胃癌及癌前疾病的指标;
5. Hp阳性伴有PGC阴性表达和低sPGA、高sPGC的患者胃疾病恶性程度高,应密切随访;
6. Hp根治成功后血清PG值显著下降; PGC表达在根治前后的肠化组、异型增生组有显著差异,提示Hp根除可以使PGC表达率增加,或许可以减慢肠化、异型增生这些癌前病变向胃癌的发展速度。
Objective Immunohistochemical method(SABC) was used to detect the expression levels of PGC in CSG,CAG,IM,DYS and GC tissue, variation in the same group before and after radical cure for Hp infection. To detect the level of sPGA, sPGC and the variation in serum pepsinogen concentration before and after Helicobacter pylori eradication by ELISA. To analyze the relationship between the PGC and Hp, the correlation between the expression of PGC and the level of sPGA, sPGC, which will help to guidance the clinical work , also further interpreted PGC may be a good molecular maker for the early diagnosis of gastric carcinoma .
Method The experiment was performed from 2008 to 2009 at the Department of Pathology in Affiliated Hospital of Medical College of Yan’an University . The expression of PGC was detected by immunohistochemistry in 49 chronic superficial gastritis(CSG), 35 chronic atrophic gastritis (CAG), 40intestinal metaplasia(IM), 39 Dysplasia (DYS)and 41gastric cancer (Ca) in 204 endoscopic biopsy specimens. To detect the level of sPGA, sPGC by ELISA. The data were analyzed for significance using the statistical software SPSS 16.0 computer package. Chi-square test was used in the analysis of enumeration data, the differences of measurement data were compared with the analysis of variance and t test, Tissue expression and serum in correlation analysis using Person. P <0.05 statistically significant.
Result
1. PGC Expression among different gastric disease tissue there were differences in PGC Expression among different gastric disease tissue, the expression of pepsinogenC decreased significantly on sequence(P<0.05 ).the positive rate of PGC is 95.9%,77.1%,55.0%,51.3%,7.3% (CSG,CAG, IM,DYS,Ca). The positive rate of PGC in CSG was significantly higher than in the others(P<0.05), The positive rate was significantly higher in CAG than in IM,DYS and Ca, but there is no significant difference between IM and DYS(P>0.05). The positive rate was significantly lower in Ca than in others(P<0.05).
2. Comparison Serum Pepsinogen Levels in patients with different gastric diseases
There were differences in concentration of sPGA, sPGC among the groups. And there was extreme significant statistics difference (P< 0.05). sPGA decreased significantly on sequence(P<0.05). sPGC increased significantly on sequence(P<0.05).sPGC in Ca is higher than in others(P<0.05),but no significant difference in serum PGC were detected in CSG,CAG, IM,DYS(P>0.05).
3. Comparisons between different expression of tissue PGC and concentration of serum PG
By the decrease of PGC expression, lesion tissue in CAG,CSG,IM,DYS,Ca, their concentration of serum PGC was increased and their sPGA concentration was decreased, and there is statistic difference(P<0.05). The sPGA decreased, the sPGC increased along with decrease of PGC expression in lesion tissue, they have good relativity and the statistic difference was similar (ra=0.956,Pa= 0.011;rc=-0.968,Pc=0.007).
4. Comparisons between different expression of tissue PGC and concenrtation of serum PG in H.p infections and non-infections
Rate of PGC expression in groups (CSG,IM,DYS,Ca) of H.p infection was lower than that of non-infection(P<0.05),but there is no statistic difference in CAG(P>0.05). The rate of PGC increased significantly on sequence in different groups of eradication successfully (P<0.05),and in IM,DYS,there is statistic difference(P<0.05), but in CAG or CSG, there is no difference(P>0.05). The difference was not statistically significant in the gruoups of eradication failure (P>0.05).
Concentration of sPGA, sPGC in groups of H.p infection was higher than that of non-infection (P<0.05). There is significantly difference of sPGC among the gruoups (P<0.05).but, only in CAG there is significantly difference of sPGA(P<0.05). Concentration of sPGA, sPGC is lower in different groups of eradication successfully than before (P<0.05), but the difference was not statistically significant in the gruoups of eradication failure (P>0.05).
Conclusion
1. the rate of PGC expression in different age and sex of gastric disease in patients with no significant differences. sPGA and sPGC is higher in male than in female, is higher in <65 guoups than in≥65 groups.
2. Tissue expression of PGC is negative to the malignant degree of gastric mucosa cell and positive with the development of gastric of gastric mucosa diseases.
3. Serum sPGA decreased obviously is an increased risk.
4. The test, which only use sPGA or sPGC to detect gastric mucosa, isn’t a marked in clinic, and at the same time the detection of sPG is relative to the tissue expression of PGC antigen, it is a convenient, economic maker to screen and diagnose gastric mucosa disease, and has some clinical value.
5. the patients with H.p infection ,low sPGA or high sPGC and negative expression of PGC should be closely followed.
6. Concentration of sPGA, sPGC is lower of eradication successfully than before (P<0.05).The rate of PGC increased significantly on sequence of eradication successfully in IM, DYS(P<0.05). It shows Hp perhaps can slow IM, DYS of these premalignant changes to the development of cancer.
引文
1. Rugge M ,Di Mario,F Cassaro M,et al .Pathology of the gastric antrum and body associated with Helicobacter pylori infection in nonulcerous atients:is the bacteriuma promoterof intestinal metaplasia Histo- pathology,1993;22(1):9.
2. Sipponen P ,Hyvarinen H .Role of Helicobacter pylori in the pathogene- sis of gastritis,peptic ulcer and gastric cancer.Scand J Gastroent- erol,1993;Suppl 196:3.
3. Kusic B,Gaspaorv S,Katicic M,et al.Monoclonality in Helicobacter pylori-positive gastric biopsies:an early detection of mucosa- associated lymphoid tissue lymphoma.Exp Mol Patbol.2003 Feb;74(1):61 -67.
4. Uemura N, Okamoto S, Yamamoto S. H. pylori infection and the dev- elopment of gastric cancer.Keio J Med,2002 Dec;51 Suppl 2:63-68.
5. Kageyama T, Ichinose M, Tsukada-Kato S, et al .Molecular cloning of neonate/infant-specific pepsinogens from rat stomach mucosa and their expressional change during development. Biochem Biophys Res Common,2 000;267:806-812
6.樊代明,张学庸,陈希陶,等.抗低分化胃癌细胞系MKN-46-9单克隆抗体的制备及免疫组化鉴定,解放军医学杂志,1988;13:12.
7.张万岱,徐智民.幽门螺杆菌感染诊断方法的评价与诊断标准,中华全科医师杂志,2004,3(6):351-353.
8. Gritti I, Banfi G, Roi GS. Pepsinogens: physiology, pharmacology pathophysiology and exercise. Pharmacol Res 2000 ,41(3):265-281
9. Korstanje A,den Hartog G,Biemond I,Lamers CB.The serological gastric biopsy:a non-endoscopical diagnostic approach in management of the dyspeptic patient:significance for primary care based on a survey of the literature. Scand J Gastroenterol 2002;(Suppl):22-26
10.李红梅,宁佩芳,袁媛.不同胃黏膜疾病胃蛋白酶原C组织原位表达与胃蛋白酶原血清学检测水平的比较.世界华人消化杂志,2005;13(20):2473-2476
11. Kitahara F , Kobayashi K, Sato T , et al. Accuracy of sreeening for gastric cancer using serum pepsinogen concentration. Gut , 1999 ,44 : 693-697.
12. Busby-Earle RM , Williams AR , Piris J . Pepsinogen in gastric carcinomas. Hum pathol ,1986 ,17 :1031-1035
13.孙丽萍,等.胃蛋白酶原基因插入-缺失多态与胃癌患者及其癌前疾病易感性的关系.中华医学杂志,2006;86(43):3059-3063
14. Fiocca R , Cornaggia M , Villani L , et al. Expression of pepsinoogenⅡin gastric cancer. Its ralatioship to local invasion and lymph node metastases. Cancer , 1988 ,61 :956-962.
15. Fernandez R , Vizoso F , Rodriguez JC , et al. Expression and prognostic significance of pepsinogen C in gastric carcinoma. Ann Surg Oncol , 2000 ,7:508-514
16. YAMAGUCHI T,TAKAHASHI T, YOKOTA T, et al.Urinary pepsinogenⅠas atumor marker of stomach cancer after total gastrictomy [J].Cancer,1991,68:906.
17. Gritti I, Banfi G, Roi GS. Pepsinogens: physiology, pharmacology pathophysiology and exercise. Pharmacol Res 2000 ,41(3):265-281
18. Mursat F. Immunocytochemistry and in situ hybridization studies of pepsinogenic C-producing cell in developing rat fundic glands.Cells Tissue Res.1998,293(1):121-131
19. Tao C, Yamamoto M, Mimo H, Inoue M, MasuJina T,Kajiyoma G. Pepsinogen secretion coupling of w 2qx exocytosis visualised by video microscopy and Ca,(2+) in single cells. Am J Physiol 1998,274:G1166-1177.
20. Richter C, Tanaka T, Yada RY.Mechanism of activation of the gastric aspartic proteinases:pepsinogen,progastricsin and prochymosin. Biochem J.1998, 335(Pt3):481-90.
21.黄飚,肖华龙,张瑞祥,等.胃蛋白酶原Ⅰ时间分辨荧光免疫分析法的建立[J].中华微生物学和免疫学杂志,2004,24(6):492-495
22.张瑞祥,黄飚,朱岚,等.胃蛋白酶原Ⅱ时间分辨荧光免疫分析法的建立[J].标记免疫分析与临床,2004,11(2):99-101
23. Zhang XH ,Bu YH ,Wang JL ,et al. Follow up observation of gastric mucosa changes in subjects with abnomal PG levels. Chin Oncol Clin ,2000,27 :491-494
24.蒋孟荣,肖志强.胃癌患者血清胃蛋白酶原含量检测及其意义[J].实用癌症杂志2000,15(1):40-42
25. Aoki K and Misumi J.Statistical analysis of serum pepsinogenⅠ(PGⅠ)andⅡ(PGⅡ)levels, PGI/PGⅡratios and serum gastrin levels in a general population[J]. Envir Health and Prev Med,1996,1:136
26. Correa P. Human gastric carcinogens is a multistep and multifactional process-first American Cancer society award lecture on cancer epidemiology and prevention.Cancer Res, 1992;83:1041-1046
27.古敬丽,血清胃蛋白酶原、幽门螺旋杆菌与萎缩性胃炎相关性探讨.河南科技大学学报(医学版).2007;25(4):260-261
28.周红凤,刘丹,吴瑾,王雯.胃蛋白酶原和胃癌相关抗原与胃癌的研究进展.世界华人消化杂志,2007;15(17):1940-1946
29.张祥宏,卜玉华,王俊灵,等.血清胃蛋白酶原异常居民胃粘膜变化的随访观察.中国肿瘤临床,2000,27(7):491-494
30. Asaka M ,e ta l.R elationshipb etweenH elicobacterp yloriin fection , atr ophicg astritisa ndg astricc arcinomain a J apanesep opulati on .E urJ G astroenterolH epatol,1 995,7(Suppl1):7-10
31.张祥宏,等.河北省赞皇县胃癌高、低发区居民血清胃蛋白酶原、胃泌素和幽门螺杆菌抗体检测,中华消化杂志,1999;3(19)
32. Di Mario F, Moussa AM, Caruana P, Merli R, Cavallaro LG, et al.‘Serological biopsy' in first-degree relatives of patients with gastric cancer affected by Helicobacter pylori infection. Scand J Gastroenterol.2003,38(12):1223-1227.
33.孙丽萍,宫月华,袁媛。血清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(8):1827-1830
34.马应杰,吴晶新.血清胃蛋白酶原与幽门螺杆菌感染.临床荟萃,1998,13(21):961-963
1.何庆泗译.胃癌.见:Vincent T. Devita主编.Cancer principles and Practice of Oncology.济南:山东科学技术出版社.2001:1056-1057.
2. Gritti I, Banfi G, Roi GS. Pepsinogens :physiology ,pharmacology pathophysiology and exercise .Pharmacol Res 2000;41:265-281.
3. Foster C, Aktar A, Kopf D, Zhang P, Guttentag S. Pepsinogen C: a type 2 cell-specific protease. Am J Physiol Lung Cell Mol Physiol 2004;286:L382-387.
4. Kageyama T, Ichinose M, Tsukada-kato S, et al.Molecular cloning of neonater/ infant-specific prpsinogens from rat stomch mucosa and their expressional change during development .Biochem Biochem Biophiys Res Commun, 2000; 267: 806-812.
5. Azuma T , Pals G , Taggart RT .RFLP for human papsinogen C gene(PGC) . Nucleic Acids Res , 1988;16:9372.
6.孙丽萍,等.胃蛋白酶原基因插入-缺失多态与胃癌患者及其癌前疾病易感性的关系.中华医学杂志,2006;86(43):3059-3063.
7.藤尺亨,熊谷俊子,後藤晓,燕森一也,赤松秦次,清研道.血清抗Hp抗体ぉょひ血清へ。フ。シノケ-ソⅠ/Ⅱ比のHp除菌判定マ-カ-としこの检讨.日本临床,1999;57:101-106.
8.姜海行,李君武,施焕中.幽门螺杆菌诱导大鼠胃黏膜细胞分泌胃蛋白酶原.中华微生物学和免疫学杂志,2001;21(4):381.
9. Ito M, Harama K, Kamada T, et al Helicobacter pylori eradication therapy improved atrophic gastritis and intestinal metaplasia :a 5-year prospective study of patients with atrophic gastritis [J] Aliment Pharmacol Ther,2002;16:1449-1456.
10. Lorente S, DoiZ O, Trinidad Serrano M, et al. Helicobacter pylori stimulates pepsinogen secretion from isolated human peptic cells.Gut,2002;50:13-18.
11. Kishi K, Kinoshita Y, Matsushima Y, et al. Pepsinogen gene product is a possible growth factor during mucosa healing. Biochemi Biophys Res Commun, 1997; 238:17-20.
12.李益农,陆星华,主编.现代临床医学丛书:消化内镜学.北京科学出版社出版,1996:252.
13.王书奎,等.胃蛋白酶原免疫放射分析在胃癌诊断中的应用.中华核医学杂志,2003;23(2):124.
14.李红涛,吴开春,李彩宁,等.血清胃蛋白酶原诊断胃体黏膜萎缩的研究.中华内科杂志,2004;43(2):141-142.
15.宁佩芳,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.中华医学杂志,2004;84(10):818-821.
16. Dinid-Ribeiro M, Yamaki G,Kmiki K,et al.Meta-analysis on the validity of pepsinogen test for gastric carcinoma,dysplasia or chronic atrophic gastritis screening [J].J Med Screen,2004;11(3):141-147.
17. Hiroshi O,Masashi O,kimihiko Y,et al.Gastric cancer screening of a high-risk population in Japan using serum pepsinogen and barium digital radiography[J].Cancer Sci,2005;96(10):713-720.
18.刘慧杰,董明,王兰,等.胃蛋白酶原C基因多态性在胃癌家系成员中的分布.基础医学与预防医学,2001;15(3):163-165.
19.林惠中,陈磊,李晓川,等.胃蛋白酶原及其亚群与CA72-4联合检测对早期胃癌诊断及预后判断的意义.中华外科杂志,2004;42(24):1505-1508.
20. Tabata H, Fuchigami T, Kobagashi H. Difference in degree of mucosal atrophy between elevated and depressal types of gastric epithelial tumors [J].Scand J Gastroenteral,2001;36:1134-1140.
21. Fernandez R, Vizoso F, Rodriguez JC, Merino AM, Gonzalez LO, Quintela I, Andicoechea A, Truan N,Diez MC. Expression and prognostic significance of pfpsinogen C in gastric carcinoma. Ann Surg oncol 2007;7:508-514.
2. Sipponen P ,Hyvarinen H .Role of Helicobacter pylori in the pathogene- sis of gastritis,peptic ulcer and gastric cancer.Scand J Gastroent- erol,1993;Suppl 196:3.
3. Kusic B,Gaspaorv S,Katicic M,et al.Monoclonality in Helicobacter pylori-positive gastric biopsies:an early detection of mucosa- associated lymphoid tissue lymphoma.Exp Mol Patbol.2003 Feb;74(1):61 -67.
4. Uemura N, Okamoto S, Yamamoto S. H. pylori infection and the dev- elopment of gastric cancer.Keio J Med,2002 Dec;51 Suppl 2:63-68.
5. Kageyama T, Ichinose M, Tsukada-Kato S, et al .Molecular cloning of neonate/infant-specific pepsinogens from rat stomach mucosa and their expressional change during development. Biochem Biophys Res Common,2 000;267:806-812
6.樊代明,张学庸,陈希陶,等.抗低分化胃癌细胞系MKN-46-9单克隆抗体的制备及免疫组化鉴定,解放军医学杂志,1988;13:12.
7.张万岱,徐智民.幽门螺杆菌感染诊断方法的评价与诊断标准,中华全科医师杂志,2004,3(6):351-353.
8. Gritti I, Banfi G, Roi GS. Pepsinogens: physiology, pharmacology pathophysiology and exercise. Pharmacol Res 2000 ,41(3):265-281
9. Korstanje A,den Hartog G,Biemond I,Lamers CB.The serological gastric biopsy:a non-endoscopical diagnostic approach in management of the dyspeptic patient:significance for primary care based on a survey of the literature. Scand J Gastroenterol 2002;(Suppl):22-26
10.李红梅,宁佩芳,袁媛.不同胃黏膜疾病胃蛋白酶原C组织原位表达与胃蛋白酶原血清学检测水平的比较.世界华人消化杂志,2005;13(20):2473-2476
11. Kitahara F , Kobayashi K, Sato T , et al. Accuracy of sreeening for gastric cancer using serum pepsinogen concentration. Gut , 1999 ,44 : 693-697.
12. Busby-Earle RM , Williams AR , Piris J . Pepsinogen in gastric carcinomas. Hum pathol ,1986 ,17 :1031-1035
13.孙丽萍,等.胃蛋白酶原基因插入-缺失多态与胃癌患者及其癌前疾病易感性的关系.中华医学杂志,2006;86(43):3059-3063
14. Fiocca R , Cornaggia M , Villani L , et al. Expression of pepsinoogenⅡin gastric cancer. Its ralatioship to local invasion and lymph node metastases. Cancer , 1988 ,61 :956-962.
15. Fernandez R , Vizoso F , Rodriguez JC , et al. Expression and prognostic significance of pepsinogen C in gastric carcinoma. Ann Surg Oncol , 2000 ,7:508-514
16. YAMAGUCHI T,TAKAHASHI T, YOKOTA T, et al.Urinary pepsinogenⅠas atumor marker of stomach cancer after total gastrictomy [J].Cancer,1991,68:906.
17. Gritti I, Banfi G, Roi GS. Pepsinogens: physiology, pharmacology pathophysiology and exercise. Pharmacol Res 2000 ,41(3):265-281
18. Mursat F. Immunocytochemistry and in situ hybridization studies of pepsinogenic C-producing cell in developing rat fundic glands.Cells Tissue Res.1998,293(1):121-131
19. Tao C, Yamamoto M, Mimo H, Inoue M, MasuJina T,Kajiyoma G. Pepsinogen secretion coupling of w 2qx exocytosis visualised by video microscopy and Ca,(2+) in single cells. Am J Physiol 1998,274:G1166-1177.
20. Richter C, Tanaka T, Yada RY.Mechanism of activation of the gastric aspartic proteinases:pepsinogen,progastricsin and prochymosin. Biochem J.1998, 335(Pt3):481-90.
21.黄飚,肖华龙,张瑞祥,等.胃蛋白酶原Ⅰ时间分辨荧光免疫分析法的建立[J].中华微生物学和免疫学杂志,2004,24(6):492-495
22.张瑞祥,黄飚,朱岚,等.胃蛋白酶原Ⅱ时间分辨荧光免疫分析法的建立[J].标记免疫分析与临床,2004,11(2):99-101
23. Zhang XH ,Bu YH ,Wang JL ,et al. Follow up observation of gastric mucosa changes in subjects with abnomal PG levels. Chin Oncol Clin ,2000,27 :491-494
24.蒋孟荣,肖志强.胃癌患者血清胃蛋白酶原含量检测及其意义[J].实用癌症杂志2000,15(1):40-42
25. Aoki K and Misumi J.Statistical analysis of serum pepsinogenⅠ(PGⅠ)andⅡ(PGⅡ)levels, PGI/PGⅡratios and serum gastrin levels in a general population[J]. Envir Health and Prev Med,1996,1:136
26. Correa P. Human gastric carcinogens is a multistep and multifactional process-first American Cancer society award lecture on cancer epidemiology and prevention.Cancer Res, 1992;83:1041-1046
27.古敬丽,血清胃蛋白酶原、幽门螺旋杆菌与萎缩性胃炎相关性探讨.河南科技大学学报(医学版).2007;25(4):260-261
28.周红凤,刘丹,吴瑾,王雯.胃蛋白酶原和胃癌相关抗原与胃癌的研究进展.世界华人消化杂志,2007;15(17):1940-1946
29.张祥宏,卜玉华,王俊灵,等.血清胃蛋白酶原异常居民胃粘膜变化的随访观察.中国肿瘤临床,2000,27(7):491-494
30. Asaka M ,e ta l.R elationshipb etweenH elicobacterp yloriin fection , atr ophicg astritisa ndg astricc arcinomain a J apanesep opulati on .E urJ G astroenterolH epatol,1 995,7(Suppl1):7-10
31.张祥宏,等.河北省赞皇县胃癌高、低发区居民血清胃蛋白酶原、胃泌素和幽门螺杆菌抗体检测,中华消化杂志,1999;3(19)
32. Di Mario F, Moussa AM, Caruana P, Merli R, Cavallaro LG, et al.‘Serological biopsy' in first-degree relatives of patients with gastric cancer affected by Helicobacter pylori infection. Scand J Gastroenterol.2003,38(12):1223-1227.
33.孙丽萍,宫月华,袁媛。血清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(8):1827-1830
34.马应杰,吴晶新.血清胃蛋白酶原与幽门螺杆菌感染.临床荟萃,1998,13(21):961-963
1.何庆泗译.胃癌.见:Vincent T. Devita主编.Cancer principles and Practice of Oncology.济南:山东科学技术出版社.2001:1056-1057.
2. Gritti I, Banfi G, Roi GS. Pepsinogens :physiology ,pharmacology pathophysiology and exercise .Pharmacol Res 2000;41:265-281.
3. Foster C, Aktar A, Kopf D, Zhang P, Guttentag S. Pepsinogen C: a type 2 cell-specific protease. Am J Physiol Lung Cell Mol Physiol 2004;286:L382-387.
4. Kageyama T, Ichinose M, Tsukada-kato S, et al.Molecular cloning of neonater/ infant-specific prpsinogens from rat stomch mucosa and their expressional change during development .Biochem Biochem Biophiys Res Commun, 2000; 267: 806-812.
5. Azuma T , Pals G , Taggart RT .RFLP for human papsinogen C gene(PGC) . Nucleic Acids Res , 1988;16:9372.
6.孙丽萍,等.胃蛋白酶原基因插入-缺失多态与胃癌患者及其癌前疾病易感性的关系.中华医学杂志,2006;86(43):3059-3063.
7.藤尺亨,熊谷俊子,後藤晓,燕森一也,赤松秦次,清研道.血清抗Hp抗体ぉょひ血清へ。フ。シノケ-ソⅠ/Ⅱ比のHp除菌判定マ-カ-としこの检讨.日本临床,1999;57:101-106.
8.姜海行,李君武,施焕中.幽门螺杆菌诱导大鼠胃黏膜细胞分泌胃蛋白酶原.中华微生物学和免疫学杂志,2001;21(4):381.
9. Ito M, Harama K, Kamada T, et al Helicobacter pylori eradication therapy improved atrophic gastritis and intestinal metaplasia :a 5-year prospective study of patients with atrophic gastritis [J] Aliment Pharmacol Ther,2002;16:1449-1456.
10. Lorente S, DoiZ O, Trinidad Serrano M, et al. Helicobacter pylori stimulates pepsinogen secretion from isolated human peptic cells.Gut,2002;50:13-18.
11. Kishi K, Kinoshita Y, Matsushima Y, et al. Pepsinogen gene product is a possible growth factor during mucosa healing. Biochemi Biophys Res Commun, 1997; 238:17-20.
12.李益农,陆星华,主编.现代临床医学丛书:消化内镜学.北京科学出版社出版,1996:252.
13.王书奎,等.胃蛋白酶原免疫放射分析在胃癌诊断中的应用.中华核医学杂志,2003;23(2):124.
14.李红涛,吴开春,李彩宁,等.血清胃蛋白酶原诊断胃体黏膜萎缩的研究.中华内科杂志,2004;43(2):141-142.
15.宁佩芳,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.中华医学杂志,2004;84(10):818-821.
16. Dinid-Ribeiro M, Yamaki G,Kmiki K,et al.Meta-analysis on the validity of pepsinogen test for gastric carcinoma,dysplasia or chronic atrophic gastritis screening [J].J Med Screen,2004;11(3):141-147.
17. Hiroshi O,Masashi O,kimihiko Y,et al.Gastric cancer screening of a high-risk population in Japan using serum pepsinogen and barium digital radiography[J].Cancer Sci,2005;96(10):713-720.
18.刘慧杰,董明,王兰,等.胃蛋白酶原C基因多态性在胃癌家系成员中的分布.基础医学与预防医学,2001;15(3):163-165.
19.林惠中,陈磊,李晓川,等.胃蛋白酶原及其亚群与CA72-4联合检测对早期胃癌诊断及预后判断的意义.中华外科杂志,2004;42(24):1505-1508.
20. Tabata H, Fuchigami T, Kobagashi H. Difference in degree of mucosal atrophy between elevated and depressal types of gastric epithelial tumors [J].Scand J Gastroenteral,2001;36:1134-1140.
21. Fernandez R, Vizoso F, Rodriguez JC, Merino AM, Gonzalez LO, Quintela I, Andicoechea A, Truan N,Diez MC. Expression and prognostic significance of pfpsinogen C in gastric carcinoma. Ann Surg oncol 2007;7:508-514.