Dose-dependent Induction of Both Pepsinogen-altered Pyloric Glands and Adenocarcinomas in the Glandular Stomach of C3H Mice Treated with N-Methyl-N-nitrosourea

The dose-response relation for the appearance of pepsinogen isozyme 1 (Pg l)-altered pyloric glands (PAPG) and the related induction of adenocarcinomas were examined in male C3H mice given N -methyl- N -nitrosourea (MNU) in their drinking water at the concentration of 120 ppm (group 1), 60 ppm (group 2), 30 ppm (group 3) or 0 ppm (group 4) for 30 weeks and then normal tap water. Animals were killed at weeks 10, 30 and 42. Adenomatous hyperplasias and adenocarcinomas were noted from week 30 and their induction was dose-dependent at week 42. Almost all cells of pyloric gland cell type in those lesions had little or no immunohistochemically demonstratable Pg 1 content, as was also the case for the cells in PAPG, whose numbers per 100 normal-appearing pyloric glands were found to be MNU dose-dependent at all experimental time points. The numbers of PAPG at week 10 significantly correlated with the incidences of adenomatous hyperplasias and adenocarcinomas at week 42. Investigation of proliferation by immunohistochemical detection of bromodeoxyuridine (BrdU) labeling in the PAPG at week 10 demonstrated elevation (P <0.05) as compared to normal pyloric glands. Intestinal metaplasia was not a feature in the present experiment and the results suggest that in mice, PAPG might be a preneoplastic lesion involved in gastric chemical carcinogenesis.     

In Situ Localization of Pepsinogens I and II mRNA in Human Gastric Mucosa

Localization of pepsinogens I and II mRNA in the human gastric mucosa was investigated by an in situ hybridization method using digoxigenin labeled cDNA probes. Gastric fundic mucosa from healthy volunteers, which was stained with digoxigenin labeled pepsinogens I and II cDNA probes, showed positive staining in the cytoplasm of both chief cells and mucous neck cells. In contrast, gastric antral mucosa stained with the pepsinogen I cDNA probe showed no positive reaction in the surface mucous cells or pyloric glands. On the other hand, the pyloric glands were stained positively with the pepsinogen II cDNA probe and the staining appeared to be identical to that obtained with the anti pepsinogens I and II monoclonal antibodies using the avidin biotin peroxidase complex technique. These results are consistent with those of previous studies that have employed immunochemical and immunohistochemical techniques. Acta Pathol Jpn 39: 765 771, 1989.     

胃蛋白酶原C基因插入-缺失多态和幽门螺杆菌感染的交互作用与胃癌发病风险

目的 探讨胃癌发生发展过程中,胃蛋白酶原C(PGC)基因插入-缺失多态与幽门螺杆菌(Hp)及其不同基因亚型菌株感染的交互作用.方法 1:1频数配伍,选择基本正常(NOR)、胃糜烂溃疡(GU)、萎缩性胃炎(AG)和胃癌(Gc)各141例,分析PGE基因多态和Hp感染的交互作用.同时选择177例Hp感染阳性者,分析PGC基因多态与不同基因亚型Hp感染的交互作用.以聚合酶链反应(MR)检测PGC基因多态型及Hp基因亚型.以酶联免疫吸附实验(ELISA)检测血清Hp-IgG抗体.结果 PGG基因多态与Hp感染两因素交互作用,PGC等位基因1纯合型、Hp-IgG阳性者罹患GU、AG和GC的OR值分别为8.69、11.16和10.61(P值分别为0.049、0.02和0.03),交互作用指数分别为5.40、6.48和4.34,归因比分别为0.721、0.770和0.697.P02基因多态与不同基因亚型Hp感染对于AG和GC患病均无交互作用.结论 GC发生发展过程中,PGC基因多态与Hp感染存在正交互作用,而与不同基因亚型Hp菌株感染无交互作用.     

辽宁庄河地区居民血清胃蛋白酶原含量检测分析

目的 检测辽宁庄河居民血清胃蛋白酶原（PG）含量，以明确其基本人群分布特征，并探讨相关影响因素。方法 利用酶联免疫吸附试验（ELISA）方法对辽宁庄河地区6990名居民进行血清PGI、PGⅡ含量检测，并计算PGI／Ⅱ比值；利用胃镜及胃黏膜组织病理学检查进行胃疾病诊断；利用ELISA法检测血清幽门螺杆菌（Hp）IgG抗体滴度。结果 辽宁庄河地区居民血清PGⅠ、PGⅡ及PGI／Ⅱ中位值分别为86．9μ／L、10．6μg／L和8．1。男性血清PGⅠ、PGⅡ（95．2μg／L、12．1μ／L）显著高于女性（79．7μg／L、9．4μg／L；P=0．000），PGⅠ／Ⅱ（7．9）显著低于后者（8．3，P=0．000）。PGI／Ⅱ随年龄增高呈阶段性显著降低。PGⅠ／Ⅱ在胃黏膜由基本正常（10．4）向非萎缩性病变（8．8）、萎缩性病变（6．6）转变过程中呈显著性降低。Hp感染者血清PGⅠ、PGⅡ（88．7μg／L，11．4μg／L）显著高于非感染者（81．4μg／L，8．4μg／L；P=0．000），PGⅠ／Ⅱ（7．7）显著低于后者（9．6，P=0．000）。以PGⅠ／Ⅱ为指标筛选胃黏膜萎缩性病变，ROC曲线下面积为0．622，最适临界值为6．9，灵敏度53．2％，特异度67．5％。多因素Logistic回归分析，男性（OR：1．151，95％CI：1．042～1．272，P=0．006）、年龄≥61岁（OR：1．358，95％CJ：1．188～1．553，P=0．000）、萎缩性病变（OR：2．075，95％CI：1．870～2．302，P=0．000）及Hp感染（OR：1．546，95％CI：1．368～1．748，P=0．000）是明显影响PGⅠ／Ⅱ水平的因素。结论 辽宁庄河居民血清PG水平呈明显偏态分布，受性别、年龄因素影响，与胃疾病和Hp感染密切相关。PGⅠ／Ⅱ较之PGⅠ和PGⅡ，更适用于胃疾病筛查。     

Helicobacter pylori infection and markers of gastric cancer risk in Alaska Native persons: A retrospective case-control study

BACKGROUND:

Alaska Native persons experience gastric cancer incidence and mortality rates that are three to four times higher than in the general United States population.

OBJECTIVE:

To evaluate pepsinogen I, pepsinogen I/II ratio, anti-Helicobacter pylori and cytotoxin-associated gene A (CagA) antibody levels, and blood group for their associations with gastric cancer development in Alaska Native people.

METHODS:

The present analysis was a retrospective case-control study that matched gastric cancers reported to the Alaska Native Tumor Registry from 1969 to 2008 to three controls on known demographic risk factors for H pylori infection, using sera from the Alaska Area Specimen Bank. Conditional logistic regression evaluated associations between serum markers and gastric cancer.

RESULTS:

A total of 122 gastric cancer cases were included, with sera predating cancer diagnosis (mean = 13 years) and 346 matched controls. One hundred twelve cases (91.8%) and 285 controls (82.4%) had evidence of previous or ongoing H pylori infection as measured by anti-H pylori antibody levels. Gastric cancer cases had a 2.63-fold increased odds of having positive anti-H pylori antibodies compared with their matched controls (P=0.01). In a multivariate model, non-cardia gastric cancer (n=94) was associated with anti-H pylori antibodies (adjusted OR 3.92; P=0.004) and low pepsinogen I level (adjusted OR 6.04; P=0.04). No association between gastric cancer and blood group, anti-CagA antibodies or pepsinogen I/II ratio was found.

CONCLUSION:

Alaska Native people with gastric cancer had increased odds of previous H pylori infection. Low pepsinogen I level may function as a precancer marker for noncardia cancer.     

血清胃功能、HP检测联合窄带成像放大内镜对胃溃疡诊断的临床价值

目的探讨血清胃功能(胃蛋白酶原Ⅰ,Ⅱ及PGR、胃泌素-17)、幽门螺杆菌(Hp)感染联合窄带成像放大内镜对胃溃疡诊断的临床应用价值。方法选择2015年10月~2016年12月于我院经窄带成像放大内镜(NBI-ME)诊断为胃溃疡、胃癌,并经病理检查确诊的患者113例,分为胃溃疡组65例和胃癌组48例,选择体检均合格的健康者65例为对照组。采用酶联免疫法测定血清胃蛋白酶原Ⅰ/Ⅱ、PGR、胃泌素-17等血清胃功能指标,采用C14呼气试验检测Hp。结果胃溃疡组和胃癌组Hp感染率均明显高于对照组,差异有统计学意义(P0.05)。与对照组比较,胃溃疡组血清PGⅠ、PGR水平显著升高(P0.05);胃癌组患者血清PGⅠ、PGR水平低于对照组(P0.05)。与胃癌组比较,胃溃疡组PGⅠ、PGR水平升高,差异有统计学意义(P0.05)。与对照组相比,胃溃疡组、胃癌组的血清G-17浓度均高于对照组(P0.05)。结论 PGⅠ、PGⅡ、G-17等血清胃功能指标联合Hp指标的测定并经过NBI-ME进一步测定在胃溃疡及胃癌诊断及预后中具有较高的参考价值。     

血清胃蛋白酶原和癌胚抗原联合检测对胃癌的诊断价值

目的：：探讨血清胃蛋白酶原I(pepsinogen I,PGI)、PGI/II比值、癌胚抗原(carcinoembryonic antigen,CEA)和三个指标联合检测对胃癌的诊断价值。方法：将171例胃部疾病患者分为胃癌组68例和胃炎组103例,健康对照组50例。血清PGI、PGII和CEA分别采用透射免疫比浊法和化学发光法,并计算PGI/II比值。绘制受试者工作特征(ROC)曲线,计算PGI、PGI/II比值、CEA和3个指标联合检测诊断胃癌的灵敏度、特异性、阳性预测值和阴性预测值。结果：胃癌组血清PGI、PGII水平和PGI/II比值显著低于胃炎组和对照组(P<0.01,P<0.05),胃炎组血清PGI水平显著低于对照组(P<0.05),胃癌组血清CEA水平显著高于胃炎组和对照组(P<0.01)。以PGI≤50μg/L、PGI/II比值≤2.5和CEA≥10.0μg/L为阳性,血清PGI、PGI/II比值、CEA和3者联合诊断胃癌的灵敏度分别为58.8%、23.5%、23.5%和58.8%,特异性分别为88.5%、88.5%、100%和76.9%,阳性预测分别为76.9%、57.1%、100%和62.5%,阴性预测值分别为76.7%、63.9%、66.7%和74.1%。血清PGI、PGI/II和CEA诊断胃癌的ROC曲线下面积分别为0.774、0.732和0.491。结论：血清PGI、PGI/II比值对胃癌诊断的灵敏度和特异性不高,血清PGI、PGI/II比值和CEA联合检测有助于胃癌和胃炎的鉴别诊断。     

血清胃蛋白酶原、CEA、CA19-9及CA72-4检测对胃癌的诊断价值探讨

目的探讨血清Ⅰ型胃蛋白酶原(PGⅠ)、Ⅱ型胃蛋白酶原(PGⅡ)、PGⅠ/PGⅡ比值、癌胚抗原(CEA)、糖类抗原19-9(CA19-9)、糖类抗原72-4(CA72-4)检测对胃癌的诊断意义。方法定量检测40例胃癌患者(均经胃镜活检病理确诊)、40例良性胃病患者(包括浅表性胃炎、十二指肠溃疡等)及40名健康体检者(正常对照组)血清PGⅠ、PGⅡ、PGⅠ/PGⅡ及CEA、CA19-9、CA72-4等肿瘤标志物的水平,比较3组间的差异。结果胃癌组PGⅠ、PGⅠ/PGⅡ比值、CEA、CA19-9、CA72-4水平与良性胃病组及正常对照组比较,差异均有统计学意义(P0.05)。受试者工作特征(ROC)曲线显示PGⅠ诊断胃癌的最佳临界值为54 ng/mL(敏感性为63.9%、特异性为79.7%、曲线下面积为0.851±0.047),PGⅠ/PG-Ⅱ比值的最佳临界值为4.5(敏感性为75%、特异性为80.6%、曲线下面积为0.788±0.056),CEA的最佳临界值为3.20 ng/mL(敏感性为56.4%、特异性为76.9%、曲线下面积为0.310±0.063),CA19-9的最佳临界值为34.05 U/mL(敏感性为54.6%、特异性为69.2%、曲线下面积为0.352±0.065),CA72-4的最佳临界值为3.18 IU/mL(敏感性为53.8%、特异性为79.5%、曲线下面积为0.344±0.065)。PGⅠ、PGⅠ/PGⅡ比值、CEA、CA19-9、CA72-4联合检测的敏感性为89.4%,明显高于各项目单项检测(P0.05)。结论 PGⅠ、PGⅠ/PGⅡ比值、CEA、CA19-9、CA72-4对胃癌具有较高的辅助诊断价值,其联合检测有助于提高胃癌阳性检测率。     

Pepsinogens I and II in Gastric Cancer: An Immunohistochemical Study Using Monoclonal Antibodies

Monoclonal antibodies were used to examine the immunohistochemical expression of pepsinogens I and II in 31 early and 76 advanced gastric cancers. Of the 107 carcinomas studied, 19 contained pepsinogen II and only 3, found exclusively in pepsinogen II-positive cases, contained pepsinogen I. Gastric cancer produces pepsinogen II more frequently than pepsinogen I, and production of the latter is significantly associated with the former. Historically, there were 54 intestinal-type and 53 diffuse-type cancers. The former produced pepsinogen II more frequently than the latter. In the diffuse type, the four pepsinogen II-positive cases were found exclusively in females. Although the pepsinogen expression was independent of the macroscopic features in advanced gastric cancer, it was found that the protruded-type early gastric cancer produced pepsinogen II more frequently than the depressed type. Incidences of pepsinogen positivity were not different between early and advanced gastric cancers or between cancers with or without lymph node metastasis, suggesting that production of pepsinogen is independent of tumor growth.     

胃蛋白酶原相关影响因素分析

目的 研究胃蛋白酶原(PG)与幽门螺杆菌(Hp)感染、性别、年龄、吸烟、饮酒等因素的关系.方法 选取2014年1月至2014年12月在我院体检的上海市健康人群22270例作为研究对象,按Hp感染、性别、年龄、吸烟、饮酒情况分别比较PGⅠ、PGⅡ、PGR(PGⅠ/PGⅡ)的水平.结果 Hp阳性组:PGⅠ、PGⅡ显著高于Hp阴性组,PGR显著低于Hp阴性组,男性PGⅠ、PGR显著高于女性,PGⅡ显著低于女性.Hp阴性组:男性PGⅠ、PGⅡ、PGR显著高于女性.随着年龄增加,PGⅠ、PGⅡ逐渐升高,有统计学差异,PGR变化不大,仅≥70岁年龄组显著低于各年龄组.吸烟组PGⅠ、PGⅡ、PGR显著高于不吸烟组,PGⅠ、PGR显著高于曾吸烟组.曾吸烟组PGⅠ、PGⅡ显著高于不吸烟组,PGR无统计学意义.饮酒组PGⅠ、PGⅡ、PGR显著高于不饮酒组.结论 胃蛋白酶原水平与幽门螺杆菌感染、性别、年龄、吸烟、饮酒均有关.