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

目的:通过对不同类型胃黏膜活检组织胃蛋白酶原C(PGC)的表达和血清胃蛋白酶原含量的检测,研究二者的匹配程度及其在胃癌筛查与诊断中的价值.方法:129例胃黏膜活检组织及其血清标本(浅表性胃炎30例,胃黏膜糜烂溃疡35例,萎缩性胃炎29例,胃癌35例),采用免疫组织化学染色检测胃黏膜标本中PGC的表达情况;采用酶联免疫吸附实验检测血清PGA(sPGA)和PGC(sPGC)含量.结果:30例浅表性胃炎PGC抗原均为阳性表达,表达率为100%,而胃黏膜糜烂溃疡、萎缩性胃炎和胃癌组PGC抗原阳性表达率分别为80.00%,34.48%和11.43%,其表达率随疾病恶性程度的增加而下降(P<0.05).sPGC、sPGA含量各组间无统计学差异,sPGA/sPGC比值从浅表性胃炎→胃黏膜糜烂溃疡→萎缩性胃炎→胃癌依次下降,分别为11.55±0.69,9.39±0.86,8.86±0.63,6.83±0.68(P<0.05).sPGA/sPGC比值随其病变组织PGC表达程度的降低而下降,具有良好的相关性(r=0.297,P=0.001).结论:PGC的组织表达与胃黏膜细胞恶性程度呈负相关.sPGA/sPGC与PGC抗原组织表达有良好的相关性,是一个方便、经济的胃癌及癌前病变筛选和诊断的指标,具有较好的临床实用价值.     

幽门螺杆菌感染和吸烟对胃腺癌患者胃蛋白酶原水平的影响

目的　探讨幽门螺杆菌 (H·pylori,简称Hp)感染和吸烟对胃腺癌 (GAC)患者胃蛋白酶原 (PG)水平的影响。方法　PGⅠ、PGⅡ水平用放射免疫法检测 ,用14 C 尿素呼气试验及ELISA法测血清抗Hp IgG抗体确定Hp感染。结果　 (1)Hp阴性吸烟的GAC患者PGⅠ水平均数明显高于Hp阴性不吸烟和曾吸烟的GAC患者 (前者t =2 70 9,P <0 0 5 ;后者t =2 15 7,P <0 0 5 ) ;Hp阳性不吸烟及曾吸烟的GAC患者 ,PGⅠ水平均数明显低于Hp阳性吸烟的GAC患者 (前者 t =2 5 37,P <0 0 5 ;后者t =2 185 ,P <0 0 5 )。 (2 )Hp阴性不吸烟及曾吸烟的GAC患者 ,其PGⅡ水平均数明显低于其Hp阳性不吸烟及曾吸烟的GAC患者 (前者 t =2 94 4 ,P <0 0 1;后者t =2 4 2 7,P <0 0 5 )。结论　吸烟可使GAC患者PGⅠ水平升高 ,停止吸烟后PGⅠ水平均数下降 ;Hp感染可提高不吸烟和曾吸烟患者PGⅡ水平     

血清胃蛋白酶原、胃泌素-17、幽门螺杆菌抗体检测在筛查胃癌风险人群中的价值分析

胃癌是目前常见的消化道恶性肿瘤之一,死亡率高.早诊早治对于胃癌患者改善预后具有重要意义.血清分子标志物凭借成本较低、简单易行、痛苦小、可动态监测等优点在胃癌及癌前疾病筛查、预后评估等方面发挥着重要的作用,在国内外临床应用较为广泛.本文就血清胃蛋白酶原、胃泌素-17、幽门螺杆菌抗体检测在筛查胃癌风险人群中的价值分析做一综...     

胃癌与十二指肠溃疡患者血清胃蛋白酶原比较

目的 比较胃癌患者与十二指肠溃疡患者血清胃蛋白酶原水平的差异及探讨其与H．pylori感染的关系。方法 采用时间分辨荧光免疫分析方法检测108例胃癌和96例十二指肠溃疡患者血清胃蛋白酶原Ⅰ、Ⅱ（PGⅠ，PGⅡ），ELISA方法检测血清H．pylori抗体。结果 胃癌和十二指肠溃疡患者之间PGⅠ水平有显著性差异，胃癌组和十二指肠溃疡组中H．pylori阳性和阴性间PGⅠ、PGⅡ、PGⅠ，PGⅡ水平等无显著性差异。结论 胃癌患者血清PGⅠ水平显著低于十二指肠溃疡患者，H．pylori感染对胃癌和十二指肠溃疡患者血清胃蛋白酶原水平和PGⅠ，PGⅡ比值均无影响。     

Effect of Helicobacter pylori infection on Bax protein expression in patients with gastric precancerous lesions

AIM: To investigate the effect of Helicobacter pylori (H pylori) infection on Bax protein expression, and explore the role of H pylori in gastric carcinogenesis. METHODS: H pylori was assessed by rapid urease test and Warthin-Starry method, and expression of Bax protein was examined immunohistochemically in 72 patients with pre-malignant lesions. RESULTS: Bax protein was differently expressed in intestinal metaplasia and gastric dysplasia, and showed 63.99% positivity. The positivity of Bax protein expression in Hpylori-positive gastric precancerous lesions (72.3%) was significantly higher than that in H pylori-negative gastric precancerous lesions (48.0%, X~2=4.191, P<0.05). H pylori infection was well correlated with the expression of Bax protein in gastric precancerous lesions (r=0.978, P<0.01). After eradication of H pylori, the positivity of Bax protein expression significantly decreased in H pylort-positive gastric precancerous lesions (X~2=5.506, P<0.05). In the persisting H pylori-infected patients, the positivity of Bax protein expression was not changed. CONCLUSION: H pylori infection may be involved in the upregulation of Bax gene, which might be one of the mechanisms of H pylori infection-induced gastric epithelial cell apoptosis. H pylori might act as a tumor promoter in the genesis of gastric carcinoma and eradication of H pylori could inhibit gastric carcinogenesis.     

Helicobacter pylori associated chronic gastritis,clinical syndromes,precancerous lesions,and pathogenesis of gastric cancer development

Helicobacter pylori(H.pylori)infection is well known to be associated with the development of precancerous lesions such as chronic atrophic gastritis(AG),or gastric intestinal metaplasia(GIM),and cancer.Various molecular alterations are identified not only in gastric cancer(GC)but also in precancerous lesions.H.pylori treatment seems to improve AG and GIM,but still remains controversial.In contrast,many studies,including meta-analysis,show that H.pylori eradication reduces GC.Molecular markers detected by genetic and epigenetic alterations related to carcinogenesis reverse following H.pylori eradication.This indicates that these changes may be an important factor in the identification of high risk patients for cancer development.Patients who underwent endoscopic treatment of GC are at high risk for development of metachronous GC.A randomized controlled trial from Japan concluded that prophylactic eradication of H.pylori after endoscopic resection should be used to prevent the development of metachronous GC,but recent retrospective studies did not show the tendency.Patients with precancerous lesions(molecular alterations)that do not reverse after H.pylori treatment,represent the"point of no return"and may be at high risk for the development of GC.Therefore,earlier H.pylori eradication should be considered for preventing GC development prior to the appearance of precancerous lesions.     

Causal role of Helicobacter pylori infection in gastric cancer

Gastric cancer is the second most frequent cancer in the world, accounting for a large proportion of all cancer cases in Asia, Latin America, and some countries in Europe. Helicobacter pylori(H pylori) is regarded as playing a specific role in the development of atrophic gastritis, which represents the most recognized pathway in multistep intestinal-type gastric carcinogenesis. Recent studies suggest that a combination of host genetic factors, bacterial virulence factors, and environmental and lifestyle factors determine the severity of gastric damage and the eventual clinical outcome of H pylori infection. The seminal discovery of H pylori as the leading cause of gastric cancer should lead to effective eradication strategies. Prevention of gastric cancer requires better screening strategies to identify candidates for eradication.     

Impact of pepsinogen C polymorphism on individual susceptibility to gastric cancer and its precancerous conditions in a Northeast Chinese population

Purpose  Human pepsinogen C (PGC) is an aspartic protease produced specifically by the gastric mucosa, and is considered as a mature marker of gastric epithelium. This study examined the contributions of PGC polymorphisms and the Helicobacter pylori (H. pylori) infection to the risk of gastric cancer (GC), and its precancerous conditions in a Northeast Chinese population. Methods  The PGC insertion/deletion polymorphism was evaluated by polymerase chain reaction analysis, followed by direct DNA sequencing in 564 cases of GC, atrophic gastritis (AG), gastric ulcer (GU) and superficial gastritis (as control). All cases were frequency-matched 1:1 by gender and age (±5). H. pylori infection was identified by serum anti-H. pylori IgG measurement through enzyme-linked immunosorbent assay. Results  Patients with a homozygous PGC allele 1 genotype had a significant risk of AG [adjusted odds ratio (OR) 3.11; 95% confidence interval (CI) 1.44–6.71] or of GC (OR 3.00; 95% CI 1.38–6.51), and a significantly elevated risk of intestinal metaplasia (OR 1.90, 95% CI 1.11–3.27). PGC polymorphism with H. pylori infection increased risk of GU (OR 8.69; 95% CI 1.01–74.69), and AG (OR 11.12; 95% CI 1.37–90.84) or GC (OR 10.61; 95% CI 1.28–87.79) in a super-multiplicative manner. The S value was 5.40, 6.48 and 4.34; and the AP value was 72.09, 7.00 and 69.69%, respectively. Conclusions  The PGC gene polymorphism increases an individual’s susceptibility to GC and its precancerous conditions. Moreover, the PGC gene polymorphism shows a positive link to H. pylori infection in the development of GC.     

血清胃蛋白酶原对胃癌的诊断价值

目的探讨血清胃蛋白酶原对胃癌的诊断价值。方法收集我院2011年6月-2011年11月经胃镜活检病理诊断浅表性胃炎27例,癌前状态51例,癌前病变8例,胃癌17例,晨起空腹采静脉血3 mL,收集血清,以酶联免疫吸附测定(ELISA)定量检测血清胃蛋白酶原Ⅰ(PGⅠ)、PGⅡ水平,计算PGⅠ/PGⅡ(PGR)值。结果在浅表性胃炎、癌前状态、癌前病变、胃癌中血清PGⅠ水平及PGR逐渐降低,而血清PGⅡ水平逐渐升高;血清PGⅠ、PGR在胃癌与浅表性胃炎、癌前状态比较差异有统计学意义,与癌前病变比较差异无统计学意义;血清PGⅡ在胃癌与浅表性胃炎、癌前状态、癌前病变比较差异均有统计学意义;胃癌与癌前疾病ROC曲线下面积PGⅠAUCROC=0.782,PGⅡAUCROC=0.919,PGR AUCROC=0.989,PGⅠ为93.53 g/L时诊断胃癌的敏感性76.47%,特异性76.27%;PGⅡ为58.85 g/L时诊断胃癌的敏感性82.35%,特异性89.83%;PGR为1.88时诊断胃癌的敏感性94.12%,特异性89.83%。结论血清PGⅠ、PGⅡ水平及PGR值对诊断胃癌有较高的敏感性和特异性,可用于胃癌筛查和早期诊断。     

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.     

H pylori and gastric cancer： Shifting the global burden

INTRODUCTION Since the discovery of H pylori in 1983, intensive research has led to the conclusion that infection with this bacterium is the major cause for the development of distal gastric cancer. Infection with the bacterium leads to a chronic inflamma…     

Effect of Helicobacter pylori VacA on gene expression of gastric cancer cells

AIM: To determine the effect of Helicobacter pylori VacA on gene expression of gastric cancer cells. METHODS: Gene expression profile of a gastric cancer cell line, SGC7901, after challenged by VacA~+ and VacA~- H pylori broth culture supernatants (BCS), was detected by the cDNA microarray technique. Cytoskeleton changes of SGC7901 and HeLa cells were observed through high-resolution laser scanning confocal microscopy. RESULTS: A total of 16 000 cDNA clones were detected. The percentage of genes with heterogeneous expression in SGC7901 cells challenged by VacA~+ BCS reached 5%, compared with that challenged by VacA~- BCS. There were 865 genes/EST with 2-fold differential expression levels and 198 genes/EST with 3-fold differential expression levels. Most of these genes were involved in vital cell events including signal transduction, regulation of gene expression, cytoskeleton, apoptosis, stress response and inflammation, cell cycle and tumor development. Cells co-cultured with VacA~+ BCS showed collapsed and disrupted microtubular cytoarchitecture. CONCLUSION: VacA~+ BCS can disrupt cytoskeletal architecture, likely through affecting the expression of cytoskeleton-associated genes, directly induce the expression of tumor promoter-related genes and inhibit the expression of tumor suppressor genes, thus favoring the development of tumors. VacA~+ BCS can also alter the expression of inflammation and stress response genes. This suggests that VacA may play an important role in the pathogenicity of H pylori.     

Standard vs magnifying narrow-band imaging endoscopy for diagnosis of Helicobacter pylori infection and gastric precancerous conditions

BACKGROUNDAdvances in endoscopic imaging enable the identification of patients at high risk of gastric cancer. However, there are no comparative data on the utility of standard and magnifying narrow-band imaging (M-NBI) endoscopy for diagnosing Helicobacter pylori (H. pylori) infection, gastric atrophy, and intestinal metaplasia. AIMTo compare the diagnostic performance of standard and M-NBI endoscopy for H. pylori gastritis and precancerous conditions. METHODSIn 254 patients, standard endoscopy findings were classified into mosaic-like appearance (type A), diffuse homogenous redness (type B), and irregular redness with groove (type C). Gastric mucosal patterns visualized by M-NBI were classified as regular round pits with polygonal sulci (type Z-1), more dilated and linear pits without sulci (type Z-2), and loss of gastric pits with coiled vessels (type Z-3). RESULTSThe diagnostic accuracy of standard and M-NBI endoscopy for H. pylori gastritis was 93.3% and 96.1%, respectively. Regarding gastric precancerous conditions, the accuracy of standard and M-NBI endoscopy was 72.0% vs 72.6% for moderate to severe atrophy, and 61.7% vs. 61.1% for intestinal metaplasia in the corpus, respectively. Compared to type A and Z-1, types B+C and Z-2+Z-3 were significantly associated with moderate to severe atrophy [odds ratio (OR) = 5.56 and 8.67] and serum pepsinogen I/II ratio of ≤ 3 (OR = 4.48 and 5.69). CONCLUSIONClose observation of the gastric mucosa by standard and M-NBI endoscopy is useful for the diagnosis of H. pylori gastritis and precancerous conditions.     

检测血清胃蛋白酶原和胃泌素-17诊断胃癌的临床价值

目的通过测定血清胃蛋白酶原(PG)Ⅰ、PGⅡ、胃泌素-17(G-17)和H.pylori-IgG抗体来预测胃癌高危,提高胃癌早诊率。方法本研究采用观察性病例-对照研究,共310例受检者纳入研究。在作血清试验前,所有患者均在胃镜下作多处活检,并根据病理结果将受检者分为胃癌组(141例,其中早期胃癌40例、进展期胃癌101例)、正常组(77例)和萎缩性胃炎组(92例)。每一例均用酶联免疫吸附试验(ELISA)定量测定空腹血清PGⅠ、PGⅡ和G-17,定性测定H.pylori-IgG抗体。结果PGⅠ和PGR(PGⅠ/PGⅡ)水平在胃癌组(28.74±11.55μg/L,1.66±1.01)明显低于正常组(123.99±32.25μg/L,10.09±1.89)和萎缩性胃炎组(58.63±25.35μg/L,4.36±2.57)(均P<0.01),根据接受者操作特征曲线(ROC)计算PGⅠ和PGR诊断胃癌的最佳界值分别为57.15μg/L(灵敏度99.3%,特异度84.5%)和2.99(灵敏度92.5%,特异度89.0%);而G-17水平胃癌组(20.86±8.24pmol/L)明显高于正常组(10.39±9.25pmol/L)和萎缩性胃炎组(8.59±6.08pmol/L)(均P<0.01)。根据ROC曲线计算G-17的最佳界值为14.61pmol/L(灵敏度75.2%,特异度71.3%)。进展期胃癌的PGⅠ和PGR水平较早期胃癌明显降低(P<0.01),而G-17差别不明显。萎缩性胃炎组和胃癌组的H.pylori-IgG抗体阳性率均明显高于正常组(P<0.01)。结论结合G-17水平明显升高而PGⅠ、PGR水平显著低下可作胃镜进行胃癌筛查,有助于提高胃癌早诊率。     

Epidemiology of Helicobacter pylori infection and gastric cancer in Asia

In Asia, the prevalence of Helicobacter pylori (H. pylori) infection varies markedly in different countries. Higher prevalence rates are found in developing Asian countries while lower rates have been reported in more industrialized and developed countries. Within a country, the seroprevalence rates may vary between distinct geographic regions. H. pylori infection is an important etiological factor for the occurrence of non‐cardia gastric adenocarcinoma. The incidence rate of gastric adenocarcinoma in Asia tends to mirror the seroprevalence rate of H. pylori infection; however, there are populations with high seroprevalence rates of H. pylori infection that paradoxically have low incidence rates of gastric adenocarcinoma. These diverse clinical outcomes are related to bacterial virulence factors, concomitant environmental factors, host susceptibility and immune response. This review summarizes the current epidemiology of H. pylori infection in Asia and analyzes these data in the context of gastric cancer epidemiology.     

PGC在不同胃疾病黏膜中的表达及与血清学水平的关系

目的:检测不同胃疾病黏膜中胃蛋白酶原(pe-psinogen C,PGC)的表达及血清sPGC、sPGA浓度,分析二者的相关性,给临床工作提供更有益信息.方法:免疫组织化学染色法检测不同胃疾病黏膜组织中PGC的表达,并结合ELISA法检测血清中sPGC、sPGA的含量.之后用SPSS16.0分析软件进行统计学处理,P<0.05具有统计学意义.结果:PGC在不同胃疾病黏膜中的表达有差异(P=0.000).浅表-萎缩-伴肠化-伴异型增生-腺癌,PGC阳性率呈现递减.sPGC、sPGA浓度在各组间比较差异有统计学意义(P=0.000,P=0.000).sPGA呈现递减,浅表组与其余各组相比差异有统计学意义(P=0.035,0.000,0.000,0.000);萎缩组与其余各组相比差异有统计学意义(P=0.000,0.000,0.031);肠化组/异型增生组与胃癌组比较差异有统计学意义(P=0.047,0.034);sPGC表现为逐渐上降趋势,胃癌组与其他各组相比差异显著(P=0.000,0.000,0.003,0.001).浅表-萎缩-肠化-异型增生-胃癌,PGC表达与sPGA呈负相关,与sPGC呈正相关(r=0.956,P=0.011vssPGA;r=-0.968,P=0.007vssPGC).结论:PGC的动态表达与胃疾病的发生发展有良好的相关性;血清sPGA明显降低提示可能与胃癌的发生发展有关;若同时进行血清PG值及组织PGC抗原表达率检测,二者具有良好的相关性,可作为临床筛查胃癌及癌前疾病的指标.     

胃癌和癌前病变中幽门螺杆菌及环氧化酶-2和p53的表达及相关性研究

[目的]检测慢性胃炎、胃癌前病变及胃癌（GGa）的胃黏膜组织中幽门螺杆菌（Hp）,环氧化酶-2（COX-2）和突变型p53的表达,探讨Hp感染在胃癌发生过程中与COX-2、p53动态表达的相关性.[方法]选择经胃镜检查及病理组织学证实为慢性浅表性胃炎（CSG）、慢性萎缩性胃炎（CAG）、肠上皮化生（IM）、不典型增生（Dys）及GCa患者各100例,快速尿素酶试验（HPUT法）和组织学改良Giemsa染色联合检测Hp,通过免疫组化检测Hp感染组和非感染组患者胃黏膜COX-2、p53.[结果]①Hp、COX-2阳性率随病变进展呈上升趋势,Hp阳性率在CAG、IM、Dys、GCa各组中显著高于CSG组（P＜0.05）;COX-2在IM、Dys、GCa各组中与慢性胃炎比较有统计学意义（P＜0.05）;②Hp感染阳性率和COX-2蛋白表达阳性率在胃癌前病变组织中存在相关性（P＜0.05）;③p53阳性率在GCa与CSG、CAG相比差异有统计学意义（P＜0.01）;④在GCa组中,Hp阳性组p53的阳性表达明显高于Hp阴性组（P＜0.05）.[结论]GCa的形成与Hp感染、突变型p53、COX-2等多种因素及其相互作用有关,可视为GCa发生的危险预警信号之一;在GCa高危人群的追踪观察和随访中,进行Hp、p53、COX-2的联合检测,对发现胃癌前病变和GCa有一定临床意义.