胃癌中幽门螺杆菌感染与原癌基因c—met表达及预后研究

目的　研究幽门螺杆菌(Hp)感染的胃癌(GC)组织中c-met表达及(Hp)感染对胃癌预后的影响。方法　经病理证实,不同病变胃粘膜145例以免疫组化检测c-met基因表达,以W-S法及快速尿素酶试验检测(Hp)感染。结果　在浅表性胃炎(CSG)、萎缩肠化生胃炎(CAG+IM)、异型增生(DYS)、早期GC和进展期GC中,c-met基因表达率分别为25.53%,51.28%,61.54%,66.67%和68.42%,CAG+IM、DYS、GC均显著高于CSG(P＜0.05)。肠型胃癌c-met阳性表达与(Hp)感染密切相关。CAG+IM,DYS和GC组c-met阳性表达(Hp)感染者明显高于阴性组。(Hp)阳性者5年生存期显著短于(Hp)阴性者。结论　(Hp)感染和c-met表达与胃粘膜增殖和恶化有关,前者也与胃癌预后有关。     

幽门螺杆菌对GC及癌前病变抑癌基因和抑制细胞凋亡基因的影响

目的 探讨幽门螺杆菌(Hp)在胃癌(GC)和癌前病变中的作用及其与抑癌基因p53、抑制细胞凋亡基因Bcl-2表达的关系.方法 选取胃镜活检标本107例,其中GC28例,异型增生(DYS)14例,肠上皮化生(IM)16例,慢性萎缩性胃炎(CAG)34例,慢性浅表性胃炎(CSG)15例.尿素酶试验和Warthin-Starry银染色检测Hp,免疫组化SP法检测p53、Bcl-2基因蛋白的表达.结果 Hp感染阳性组中GC和癌前病变的发生率高于Hp感染阴性组(P<0.05),p53、Bcl-2的阳性表达率在GC、DYS和IM中明显高于CSG(P均<0.05).结论 Hp与GC发生关系密切,持续Hp感染所致的慢性炎症可引起胃黏膜损伤,促进了p53基因的突变和Bcl-2基因的表达.     

胃癌中幽门螺杆菌感染与胃粘膜增殖及凋亡研究

目的研究幽门螺杆菌(Hp)感染的胃癌(GC)发展中增殖细胞核抗原(PCNA)表达及细胞凋亡的关系和对胃癌预后意义。方法145例经病理证实,不同胃黏膜病变采用免疫组化检测PCNA基因表达及Warthinstarry法检测Hp感染。采用原位末端标记法(TUNEL)检测细胞凋亡。结果在浅表性胃炎(CSG)、萎缩肠化生胃炎(CAG+IM)、异型增生(DYS)、早期GC和进展期GC中,PCNA基因表达率分别为24.53%,46.28%,60.54%,57.67%和71.42%,CAG+IM、DYS、GC均显著高于CSG(P<0.05)。凋亡指数(AI)分别为(4.55±2.33)%、(6.43±5.60)%、(6.45±5.12)%、(6.55±4.80)%、(8.84±5.63)%,进展期GC显著高于CSG(P<0.05)。胃黏膜凋亡指数与PCNA表达强度有密切相关(P<0.05)。PCNA阳性表达与胃癌组织类型、浆膜浸润和淋巴结转移密切相关,而且BorrmannIV明显高于早期胃癌和BorrmannI,II(P<0.05)。PCNA阳性表达与肠型胃癌Hp感染有关。CAG+IM,DYS和GC组PCNA阳性表达中Hp感染者明显高于阴性者。Hp阳性者5年生存期显著短于Hp阴性者。结论Hp感染和PCNA表达与胃黏膜增殖和恶化有关,且与凋亡有相关性。Hp感染与胃癌预后有关。     

胃癌中幽门螺杆菌感染与癌基因蛋白表达及细胞凋亡研究

目的　研究幽门螺杆菌 (Hp )感染的胃癌 (GC)发展中c -met蛋白表达及细胞凋亡的关系和对胃癌预后意义。方法　 14 5例经病理证实 ,不同胃黏膜病变采用免疫组化检测c -met基因表达及Warthin -starry法检测Hp感染。采用原位末端标记法 (TUNEL)检测细胞凋亡。结果　在浅表性胃炎 (CSG)、萎缩肠化生胃炎 (CAG +IM)、异型增生 (DYS)、早期GC和进展期GC中 ,c-met基因表达率分别为 2 5 5 3% ,5 1 2 8% ,6 1 5 4 % ,6 6 6 7%和 6 8 4 2 % ,CAG +IM、DYS、GC均显著高于CSG(P <0 0 5 )。凋亡指数 (AI)分别为 (4 5 5± 2 33) %、(6 4 3± 5 6 0 ) %、(6 4 5± 5 12 ) %、(6 5 5± 4 80 ) %、(8 84±5 6 3) % ,进展期GC显著高于CSG(P <0 0 5 )。胃黏膜凋亡指数与c -met表达强度有密切相关 (P <0 0 5 )。c -met阳性表达与胃癌组织类型、浆膜浸润和淋巴结转移密切相关 ,而且BorrmannIV明显高于早期胃癌和BorrmannⅠ ,Ⅱ (P <0 0 5 )。Hp阳性者 5年存期显著短于Hp阴性者。 结论　Hp感染和c-met表达与胃黏膜增殖和恶化有关 ,且与凋亡有相关性。Hp感染与胃癌预后有关。     

Hp感染与胃癌和癌前病变中p53、ras、c-myc基因表达的关系

目的研究幽门螺杆菌（Hp）感染与胃癌（GC）和癌前病变中p53、ras、c-myc基因表达的关系,以探讨其致病机制。方法用美兰和W-S特殊染色方法确定Hp感染,免疫组化SP法检测p53、ras、c-myc基因的表达。结果慢性萎缩性胃炎（CAG）、肠化生（IM）、异型增生（DYS）、GC的Hp感染率均高于慢性浅表性胃炎（CSG）（P均〈0.05）;p53、ras、c-myc基因在GC、DYS中的表达均高于CAG（P均〈0.05）,p53、ras基因在IM中的表达均高于CAG（P〈0.05）;IM中Hp阳性者的p53阳性表达率高于Hp阴性者（P〈0.05）,DYS、GC中Hp阳性者p53、ras、c-myc的表达率高于Hp阴性者（P均〈0.05）。结论Hp感染可能通过调节p53、ras、c-myc基因的表达而促进GC的发生。     

胃癌中幽门螺杆菌感染与癌基因蛋白表达及凋亡

目的　研究幽门螺杆菌 (Hp)感染的胃癌 (GC)发展过程中c met蛋白表达与细胞凋亡的关系及对胃癌预后的意义。方法　对 14 5例经病理证实的不同胃粘膜病变采用免疫组化法检测c met基因表达及Warthin starry法检测Hp感染。采用原位末端标记法 (TUNEL)检测细胞凋亡。结果　在浅表性胃炎 (CSG)、萎缩肠化生胃炎 (CAG +IM )、异型增生 (DYS)、早期GC和进展期GC中 ,c met基因表达率分别为 2 5 .5 3 %、5 1.2 8%、6 1.5 4%、6 6 .6 7%和 6 8.42 % ,CAG +IM、DYS、GC的c met基因表达率均显著高于CSG (P <0 .0 5 )。凋亡指数 (AI)分别为( 4 .5 5± 2 .33) %、( 6 .43± 5 .6 0 ) %、( 6 .45± 5 .12 ) %、( 6 .5 5± 4.80 ) %和 ( 8.84± 5 .6 3) % ,进展期GC显著高于CSG(P <0 .0 5 )。胃粘膜凋亡指数与c met表达强度密切相关 (P <0 .0 5 )。c met阳性表达与胃癌组织类型、浆膜浸润和淋巴结转移密切相关 ,而且BorrmannⅣ明显高于早期胃癌和BorrmannⅠ ,Ⅱ (P <0 .0 5 )。Hp阳性者 5年生存期显著短于Hp阴性者。 结论　Hp感染和c met表达与胃粘膜增殖和恶化有关 ,且与凋亡有相关性。Hp感染与胃癌预后有关。     

胃癌变过程中Hp感染与凋亡基因Survivin表达的关系

目的 研究胃癌变过程中幽门螺杆菌（Hp）感染与凋亡基因Survivin表达、细胞凋亡的关系。方法用快速尿素酶法、W—S银染法和美蓝法联合检测62例慢性浅表性胃炎（CSG）、55例慢性萎缩性胃炎（CAG）、52例肠化生（IM）、46例不典型增生（AH）、65例胃癌（Gc）组织中Hp的感染情况,采用免疫组化及TUNEL法分别检测Survivin蛋白的表达及细胞凋亡情况。结果Hp感染率、Survivin蛋白阳性表达率均随着GC形成中病变恶性程度的加重而明显上升（P〈0．05）。CAG、IM、AH和GC组Hp感染率较CSG组,Gc组较CAG组均明显升高（P均〈0．05）;AH、GC组Survivin蛋白阳性表达率明显高于IM和CAG组（P均〈0．01）;AH、GC组Hp阳性患者Survivin蛋白表达率均高于Hp阴性者（P均〈0．05）;CAG、IM、AH、GC组中Survivin阳性者凋亡指数均低于Survivin阴性者（P〈0．05）;低未分化GC患者Survivin蛋白表达明显高于高中分化者（P均〈0．05）。结论在胃黏膜癌变过程中,Hp感染可能通过逐渐上调Survivin基因的表达、抑制细胞凋亡和分化而发挥致癌作用。     

幽门螺杆菌与胃癌前病变的关系

同期检出的胃粘膜病变共302例，其中慢性浅表性胃炎(CSG)132例；慢性萎缩性胃炎(CAG)96例；肠上皮化生(IM)51例；异型增生(DYS)23例。每例于胃窦大小弯侧，胃体大小弯则取粘膜组织4块，分别进行HE染色病理检查和Hp染色的Warthin-starry染色。以镜下见到棕黑色典型Hp菌体为Hp阳性。     

胃癌变过程中Bcl-2 mRNA与幽门螺杆菌感染及细胞凋亡的关系

目的探讨胃癌变过程中Bcl-2 mRNA的表达与幽门螺杆菌(Hp)感染的相关性及其与细胞凋亡的关系。方法采用实时荧光定量逆转录—聚合酶链反应(Real-time PCR)检测62例慢性浅表性胃炎(CSG)、55例慢性萎缩性胃炎(CAG)、52例肠化生(IM)、46例不典型增生(AH)、65例胃癌(GC)组织(分别为CSG组、CAG组、IM组、AH组、GC组)中Bcl-2 mRNA的表达;快速尿素酶法、Warthin-Starry银染法和甲苯胺蓝染色联合检测胃黏膜Hp感染;原位末端标记法(TUNEL)检测胃黏膜细胞凋亡指数(AI)。结果 CSG组、CAG组、IM组、AH组、GC组胃黏膜组织中Bcl-2 mRNA阳性表达率分别为22.6%(14/62)、30.9%(17/55)、40.4%(21/52)、58.7%(27/46)、69.2%(45/65),Bcl-2 mRNA相对表达水平分别为0.095±0.015、0.115±0.012、0.173±0.027、0.224±0.042、0.368±0.036,IM组、AH组、GC组Bcl-2 mRNA表达均高于CSG、CAG组(P均<0.01),AH组高于IM组(P<0.01),GC组高于IM、AH组(P均<0.01)。Bcl-2 mRNA的表达量与胃黏膜细胞AI呈负相关(rs=-0.700,P<0.05);IM组、AH组、GC组Hp阳性患者胃黏膜细胞中Bcl-2 mRNA的表达均高于Hp阴性患者(P<0.05或0.01)。结论在胃黏膜癌变过程中,Hp感染能上调胃黏膜细胞中Bcl-2 mRNA表达,从而抑制异形细胞凋亡而发挥致癌作用。     

胃癌及癌前病变中P57~(KIP2)和PCNA的表达

探讨P57KIP2和PCNA在胃癌及癌前病变中的表达及意义。方法采用免疫组织化学技术SP法,检测P57KIP2和PCNA在57例胃癌(GC)、7例不典型性增生(Dys)、16例肠上皮化生(IM)、15例慢性萎缩性胃炎(CAG)及10例慢性浅表性胃炎(CSG)中的表达情况,并分析与胃癌临床病理之间的关系。结果P57KIP2在GC、Dys、IM、CAG、CSG中阳性表达率分别为43.9%、57.1%、81.3%、80.0%、80.0%,GC和Dys组的P57KIP2阳性表达率明显低于IM、CAG、CSG组(P均0.05);PCNA在GC、Dys、IM、CAG、CSG组阳性表达率分别为80.7%、85.7%、75.0%、46.7%、30.0%,GC、Dys、IM组PCNA表达率明显高于CAG、CSG组(P0.05);P57KIP2和PCNA均与胃癌组织分化程度相关(P0.05),而与淋巴结转移、浸润、临床分期无显著相关性(P0.05)。结论在胃黏膜癌变过程中,P57KIP2蛋白的失活不是一个早期基因事件,随着病变进展PCNA表达逐渐增加,P57KIP2蛋白表达下降和PCNA的表达增高可能在胃癌的发生发展中起重要作用,两者共同检测有助于胃癌恶性程度的判定。     

Expression of ornithine decarboxylase in precancerous and cancerous gastric lesions

AIM: To investigate the expression of ornithine decarboxylase (ODC) in precancerous and cancerous gastric lesions. METHODS: We studied the expression of ODC in gastric mucosa from patients with chronic superficial gastritis (CSG,n = 32),chronic atrophic gastritis CAG,n = 43; 15 with and 28 without intestinal metaplasia (IM),gastric dysplasia (DYS,n = 11) and gastric cancer (GC,n = 48) tissues using immunohistochemical staining. All 134 biopsy specimens of gastric mucosa were collected by gastroscopy. METHODS: The positive rate of ODC expression was 34.4%,42.9%,73.3%,81.8% and 91.7% in cases with CSG,CAG without IM,CAG with IM,DYS and GC,respectively (P < 0.01),The positive rate of ODC expression increased in the order of CSG < CAG (without IM) < CAG (with IM) < DYS and finally,GC. In addition,ODC positive immunostaining rate was lower in well-differentiated GC than in poorly-differentiated GC (P < 0.05). CONCLUSION: The expression of ODC is positively correlated with the degree of malignity of gastric mucosa and development of gastric lesions. This finding indicates that ODC may be used as a good biomarker in the screening and diagnosis of precancerous lesions.     

胃癌幽门螺杆菌感染中c-met基因表达与增殖的关系及其预后

目的 研究c-met基因蛋白及增殖细胞核抗原（PCNA）在幽门螺杆菌（Hp)感染的胃黏膜病变演进中的表达及关系，探讨Hp感染对胃癌预后的意义。方法 采用免疫组织化学法检测145例经病理证实不同胃黏膜病变的c-met和PCNA基因表达，Warthin-Starry法检测Hp感染。结果 在浅表性胃炎（CSG）、萎缩肠化性胃炎、异型增生（DYS）、早期胃癌和进展期胃癌中，c-met和PCNA2种基因在萎缩肠化性胃炎、DYS、胃癌均显著高于CSG（P＜0．05）。对胃黏膜增殖程度与c-met和PCNA阳性表达强度的密切关系分析，表明两者有显著关联（P＜0．01）。c-met和PCNA阳性表达与胃癌组织类型、浆膜浸润和淋巴结转移密切相关，而且Borrmann Ⅳ明显高于早期胃癌（P＜0．05）。c-met－LI和PCNA－LI在胃癌中等级相关表达有极显著的相关性（P＜0．001）。c-met阳性表达与肠型胃癌Hp感染有关。萎缩肠化性胃炎、DYS和胃癌组c-met阳性表达中Hp感染者明显高于阴性者。Hp阳性者5年生存期显著短于Hp阴性者。结论 c-met和PCNA基因表达与胃黏膜增殖和恶化有关，c-met基因可能成为评估胃癌恶化和预后的1项新的重要指标。Hp感染和c-met表达与胃黏膜增殖和恶化有关，Hp感染与胃癌预后有关。     

幽门螺杆菌相关胃疾病组织中P53、iNOS的表达

目的通过检测慢性浅表性胃炎、慢性萎缩性胃炎、肠上皮化生、不典型增生、胃癌组织幽门螺杆菌（Hp）和P53、一氧化氮合成酶（iNOS），探讨Hp感染与P53、iNOS表达的关系，以及Hp感染导致胃癌的可能分子机制。方法应用快速尿素酶试验和组织切片革兰氏染色和血清HpCagA抗体检测Hp，用免疫组化SP法检测上述组织的P53、iNOS。结果慢性浅表性胃炎、慢性萎缩性胃炎、肠上皮化生、不典型增生、胃癌组织中Hp检出率分别为45．9％、68．4％、71．4％、75．O％、54．8％，病变各组中P53和iNOS表达阳性率与浅表性胃炎组比较均有显著性差异。除浅表性胃炎组、萎缩性胃炎Hp阳性组的P53表达阳性率外，各病变Hp阳性组的P53和iNOS表达阳性率与各组的Hp感染阳性率呈正相关，各病变组中Hp（＋）组的P53和iNOS表达阳性率显著高于Hp（-）组，均有显著性差异。结论Hp与P53和iNOS阳性表达有一定的相关性。     

Correlations among Helicobacter pylori infection and the expression of cyclooxygenase‐2 and vascular endothelial growth factor in gastric mucosa with intestinal metaplasia or dysplasia

Background and Aims: To examine the rate of Helicobacter pylori infection and the expression of cyclooxygenase‐2 (COX‐2) and vascular endothelial growth factor (VEGF) in gastric mucosa with intestinal metaplasia or dysplasia, and explore their correlations in precancerous gastric lesions. Methods: A total of 172 patients were included in the study. H. pylori infection was evaluated by hematoxylin–eosin and modified Giemsa staining. The expression of COX‐2 and VEGF proteins was detected by immunohistochemistry. Results: The rates of H. pylori infection in gastric mucosal dysplasia (DYS), intestinal metaplasia in gastric mucosa (IM), chronic atrophic gastritis (CAG) and chronic superficial gastritis (CSG) patients were significant differences (P = 0.001). The average optical density (AOD) values of COX‐2 staining in CSG, CAG, IM and DYS patients were 13.81 ± 5.53, 45.28 ± 21.44, 73.67 ± 26.02 and 91.23 ± 45.11, respectively, with significant differences among CSG, CAG and IM patients (P = 0.037, 0.001 and 0.047 for CSG vs CAG, CSG vs IM and CAG vs IM, respectively). The expression level of VEGF in DYS patients was significantly higher than those in other patients (P = 0.001, 0.001 and 0.001 for DYS vs CSG, DYS vs CAG and DYS vs IM, respectively). The expression levels of COX‐2 in H. pylori‐positive IM, CAG and DYS patients were significantly higher than those in H. pylori‐negative counterparts (P = 0.043, 0.009, 0.001, respectively). Additionally, the expression level of COX‐2 was positively correlated with that of VEGF with the aggravation of gastric mucosal lesions (r = 0.640, P = 0.006). Conclusion: H. pylori infection might be able to induce the expression of COX‐2 in precancerous gastric lesions, which in turn upregulates the expression of VEGF.     

Expression of polycomb protein EZH2 in multi-stage tissues of gastric carcinogenesis

OBJECTIVE: To study the role and significance of the polycomb group (PcG) protein EZH2 (enhancer of zeste homolog 2) in the multi-step process of intestinal-type gastric carcinogenesis. METHODS: Gastric specimens were obtained from 142 patients with gastric disease, including 34 with chronic non-atrophic gastritis (NCAG), 33 chronic atrophic gastritis (CAG) with intestinal metaplasia (IM), 40 CAG with dysplasia (DYS) and 35 with intestinal-type gastric carcinomas (GC), and 32 Helicobacter pylori-negative controls. The EZH2 protein was stained by the immunohistochemical method and was expressed as the intensity and percentage of the total number of epithelial cells. The chronic gastritis and the grading of dysplasia were classified according to Chinese National Consensus on chronic gastritis and the Padova international classification. RESULTS: The EZH2 protein levels in the specimens of normal gastric tissue, NCAG, CAG with IM, DYS and intestinal-type GC were gradually increased (P < 0.05), but statistical significance was not found between the groups of DYS and GC. CONCLUSION: PcG protein EZH2 plays an important role in the multi-step process of intestinal-type gastric carcinogenesis.     

Metabolomic phenotype of gastric cancer and precancerous stages based on gas chromatography time-of-flight mass spectrometry

Background and Aim: To study the low‐molecular‐weight metabolites in blood plasma of patients with the progressive disease, gastric cancer, and to characterize different stages from chronic superficial gastritis (CSG) to chronic atrophic gastritis (CAG), intestinal metaplasia (IM), gastric dysplasia (DYS) and finally gastric cancer (GC). Methods: We applied gas chromatography time‐of‐flight mass spectrometry (GC/TOF‐MS) to determine metabolites levels in plasma obtained from 80 patients including 19 with CSG, 13 with CAG, 10 with IM, 15 with DYS and 22 with GC (nine preoperation and 13 postoperation). Principal component analysis (PCA) and statistics were used to differentiate the stages and to identify the markers of gastric cancer. Results: Totally, 223 peaks were detected in GC/TOF‐MS and 72 compounds were authentically identified. CSG showed distinct difference from the other groups of CAG, IM, DYS and GC, whose plots clustered closely. IM clustered closely to GC, suggesting similar metabolic patterns of them. Fifteen identified metabolites contributed most to the differentiating between CSG and GC, and characterized different stages of GC. Statistics revealed elevated levels of 2‐Hydroxybutyrate, pyroglutamate, glutamate, asparagine, azelaic acid, ornithine, urate, 11‐eicosenoic acid, 1‐monohexadecanoylglycerol and γ‐tocopherol, while downregulation of creatinine, threonate in GC group, indicating that GC patients were obviously involved in oxidative stress, and perturbed metabolism of amino acids and fatty acids. Conclusion: The metabolic phenotype of CSG is significantly different from GC, while that of IM is similar to it. The discriminatory metabolites characterizing progressive stages from CSG to GC might be the potential markers to indicate a risk of GC.     

幽门螺杆菌相关性胃病的细胞增殖和凋亡

目的 观察幽门螺杆菌（Hp)及其CagA基因对细胞增殖和凋亡的影响,进而探讨Hp增加胃癌发生危险性的机制。方法 研究对象为慢性浅表性胃炎（CSG）、慢性萎缩性胃炎（CAG）、慢性萎缩性胃炎伴肠上皮化生（CAGIM）、不典型增生（DYS）、胃癌（GC）患者127例及正常对照组（NS）14例。应用ki-67免疫组化技术评价幽门窦上皮细胞增生,用切口末端标记法（TUNEL）检测胃上皮细胞凋亡,应用聚合酶链反应（PCR）技术检测Hp的CagA基因。结果 Hp阳性患者的增殖指数（LI）和凋亡指数（AI）显著高于Hp阴性者或正常对照（P＜0．05和P＜0．01）。CSGHp阳性的LI和AI明显高于Hp阴性者（P＜0．01）,而其余四种胃病Hp阳性患者（P＜0．05）。Hp阳性或阴性CSG、NS组的AI与LI呈正相关,GC患者的AI与LI呈负相关。LI和AI与胃粘膜炎症程度无明显关系。结论 Hp诱导胃粘膜上皮细胞过度增殖和凋亡主要发生在Hp感染的早期,CagA^ Hp与CagA^－Hp促增殖和凋亡作用的能力明显不同,Hp感染通过引起增殖和凋亡比例的失调,最终促进肿瘤发生。