Expression of nuclear factor-kappa B and target genes in gastric precancerous lesions and adenocarcinoma： Association with Helicobactor pylori cagA （＋） infection

AIM:To examine the expression of nuclear factor kappaB (NF-κB) and its target genes in intestinal metaplasia (IM),dysplasia (DYS) and gastric carcinoma (GC) infected with Helicobacter pylori (H pylori) and to investigate the mechanism underlying Hpyloricytotoxin associated gene A(cag A) infection leading to gastric adenocarcinoma.METHODS: Expressions of NF-κB/p65 and its target genes:c-myc, cyclinD1 and bcl-xl were immunohistochemically examined in 289 cases of gastric biopsy and resection specimens from patients with IM, DYS and GC infected with H pylori. H pylori in the above mentioned tissues was detected by Warthin-Starry stain and rapid urease tests.IgG antibody to cagA in sera of the patients was measured by ELISA.RESULTS:The positive rates of NF-κB/p65 were significantly higher in groups with cagA of IMI-Ⅱ(28/33), IM III(48/52),DYSI(27/31), DY5 Ⅱ-Ⅲ(28/32), GC(35/40) than in groups without cagA of IMI-Ⅱ(4/17), IMⅢ(3/20), DYSI(3/20),DYSⅡ-Ⅲ(6/21), GC(10/23). The expressions of c-myc,cyclinD1, and bcl-xl were significantly higher in groups with cagA of IM Ⅲ(47/52, 49/52, 46/52), DYSⅡ-Ⅲ(29/32, 26/32,25/32) than in groups without cagA of IM Ⅲ(8/20, 7/20,5/20), DYSⅡ-Ⅲ(10/21, 8/21, 3/21), which were in conformity with the expression of NF-κB in IM Ⅲ, and DYSⅡ-Ⅲ. Asignificantly higher expression level of NF-κB/p65, c-myc,cyclinD1 and bcl-xl was detected in intestinal type GC(27/28,18/28, 22/28, 24/28) than in diffuse type GC(8/12, 3/12,3/12, 6/12), respectively.CONCLUSION: There may be two different molecular mechanisms in the occurrence of intestinal and diffuse type gastric carcinomas. Intestinal type gastric carcinoma is strongly associated with high expression of c-myc, cyclinD1 and bcl-xl through NF-κB/p65 activated by Hpylori cagA.Inhibiting the activity of NF-κB is an effective and promising way to prevent intestinal type gastric carcinoma.     

Anti-Helicobacter pylori immunoglobulin G （IgG） and IgA antibody responses and the value of clinical presentations in diagnosis of H.pylori infection in patients with precancerous lesions

AIM: To determine the prevalence of Helicobacter pylori(H. pylon) infection, the serum anti-H, pylori immunoglobulin G (IgG) and IgA antibody responses, and the value of clinical presentations in diagnosis of H. pylori infection in patients with gastric atrophy, intestinal metaplasia and dysplasia.METHODS: H. pylori infection was detected by histology in 209 patients with mild chronic atrophic gastritis (CAG, n=76),severe CAG (n=22), mild intestinal metaplasia (IM, n=22),severe IM (n=58), or dysplasia (DYS, n=31). Serum anti-H. pylori IgG and IgA were double sampled and evaluated by enzyme-linked immunoadsordent assays. 35 clinical presentations were observed and their relationship with H.pylori infection was analyzed by the k-means cluster method.RESULTS: Both IgG and IgA levels in H. pylori positive patients were significantly higher than those negative for H.pylori(P<0.001-0.01). The prevalence of H. pyloriwas highest in severe IM (84.5%), and lowest in mild CAG (51.3%)(P<0.01). They were similar in severe CAG (68.2%), mild IM (72.7%), and DYS (67.7%). In H. pyloripositive patients,the IgG levels in severe CAG were significantly higher than those in mild CAG (P<0.01). In H. pylorinegative patients,both IgG and IgA levels increased remarkably in severe IM,compared to those in mild IM (P<0.01-0.05). H. pyhri infection exhibited no association with patient‘s gender (62.1% inmales; 71.7% in females) and age (r=0.0814, P=0.241).The diagnostic accuracy based on 35 clinical presentations was 65.7%. It could be improved by 5.7% when only the assemblage of digestive symptoms were engaged, or by 8.6% when the pathogenic factors, general status and grossoscopy were combined. The diagnostic accuracy could be decreased when only the general symptoms were engaged, or when the pathogenic factors were accompanied with some common digestive symptoms.CONCLUSION: H. pylori infection is a major risk factor for the process from atrophy, IM to DYS of gastric mucosa.Serum IgG and IgA are good indicators to evaluate this progress with a certain arrearage. Investigation on the effective assemblages of clinical presentations may provide a better understanding in the pathogenesis, diagnosis and treatment for H. pyloriinfection.     

cagA and vacA genotype of Helicobacter pylori associated with gastric diseases in Xi＇an area

AIM: To establish stock of clinical Helicobacter pylori (H.pylon) isolates, to perform cagA and vacA typing of these isolates, to evaluate the relationship between genotypes of cagA and vacA and upper gastrointestinal diseases and to assess the association of vacA genotypes with presence of the pathogenicity marker-cagA.METHODS: Clinical H.pylori strains were isolated from the antrum of 259 patients in Clumbia agar. The isolated H.pylori strains were identified by histology, and16SrRNA PCR.CagA genotypes were detected by colony hybridization, the probe was derived from the cloned plasmid PcagA, and digested by EcoRI-HindⅢ and the isolated PcagA DNA fragment was radioactively labelled by the random priming method. vacA genes types (s,m)and subtypes (s1a, s1b,s2) were typed by PCR. Vacuolating toxin was detected with neutral red absorb test. The results were treated statistically by χ2test, ttest, and rank sum test.RESULTS: A total of 192 clinical H. pylori strains were isolated and the stock of Helicobacter pylori was established. The total positive rate of cagA was 87 % in all gastric diseases,and 95 % in gastric cancer group. There was a difference between gastric cancer group and the other groups (P＜0.05)except duodenal ulcer group. The expression of type s1 of vacA was more than type s2 (P＜0.05), and, the expression of type m1 was equal to type m2. In gastric cancer group,there was a difference between s1a and s1b (P＜0.05), and s1a was more than s1b. Vacuolating toxins were more in Xi′an area isolates.CONCLUSION: The cagA+ vacA type s1 clinical isolates are more in Xi′an area, but this can not serve as an index to predict gastric 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…     

Ultrastructure and molecular biological changes of chronic gastritis， gastric cancer and gastric precancerous lesions： a comparative study

AIM: To carry out a comparative study on ultrastructure and molecular biological changes of chronic gastritis (CG),gastric cancer (GC) aand gastric precancerous lesions.METHODS: By the use of histochemical staining, SEM with EDAX, TEM with EDAX, image analysis technique, RIA and chemiluminescence method, gastric mucosa of 168 patients were synchronously analyzed in morphology, trace elements, DNA, cAMP, SOD, 3H-TdR LCT and serum LPO were also done.RESULTS: The incidence of epithelial nucleoplasmic ratio ＞1, lobulated nuclei, inter-chromatin aggregation of granules, nucleolar hypertrophy, and the content of DNA,Zn, Cu in nuclei and serum LPO of each group were showed as belows: normal control group (0.0, 0.0, 6.7, 0.0, 12.6±2.7,7.6±0.4, 58.4±0.3, 2.6±0.6), CSG group (5.7, 2.9, 7.4, 2.9,15.2±3.1, 8.1±0.5, 58.9±0.5, 4.2±0.7), CAG group (31.3,29.7, 45.3, 42.2, 16.5±3.1, 8.6±0.4, 59.3±0.5, 4.5±0.6), CA group (100.0, 100.0, 72.2, 50.0, 30.7±8.2, 8.8±0.3, 59.5±0.4,6.8±1.6), ATP++group (61.5, 38.5, 23.1, 38.5, 23.5±8.9,8.3±0.4, 59.1±0.4, 5.1±1.2), IM+++ ATP++group (77.8, 55.5,33.3, 44.4, 25.1±7.2, 8.4±0.5, 59.5±0.4, 6.5±1.1),IM++++ATP++ group (100.0, 100.0, 75.0, 62.5, 28.5±9.1,8.9±0.5, 59.7±0.4, 7.6±0.7), IMⅡb group (100.0, 62.5, 75.0,50.0, 27.3±10.3, 8.6±0.3, 59.5±0.4, 6.1±0.9); whereas the content of Zn, Cu in mitochondria and cAMP, SOD in gastric mucosa, and 3H-TdR LCT of each group were showen as belows: normal control group (9.2±0.5, 58.3±0.3, 15.9±1.5,170.5±6.1, 1079.7±227.4), CSG group (8.6±0.5, 57.8±0.3,14.6±1.8, 163.3±5.6, 867.3±240.5), CAG group (8.3±0.4,57.5±0.3, 13.4±1.8, 161.2±4.3, 800.9±221.8), CA group (8.9±0.4, 57.1±0.3, 10.2±3.9, 152.2±3.8, 325.7±186.8),ATP++ group (9.1±0.4, 57.0±0.3, 12.4±1.8, 161.5±3.8,642.9±174.3), IM+++ ATP++ group (8.6±0.4, 56.9±0.3,12.0±2.3, 152.2±2.5, 326.3±160.3), IM++++ATP++ group (8.5±0.3, 56.8±0.2, 10.4±0.9, 147.4±2.6, 316.1±170.7),IMⅡb group (8.6±0.3, 56.9±0.3, 11.9±1.9, 150.0±2.8,318.9±145.8), there were significant differences between groups (P＜0.05-0.01).CONCLUSION: There was a significant difference between CG and GC in their ultrastructure and molecular biology.Only on the condition of changes of internal environment in combination with the harmful effect of external environment, chronic atrophic gastritis can then develop into gastric cancer. Hence it might have similar epithelial cell ultrastructure and molecular biological changes in ATP++, IMⅡb and cancer, hence there were similar patterns of occurrence, development and transformation.Recognition of this trend might help to explore problems of prevention and cure.     

Prevalence of H pylori associated ‘high risk gastritis＇ for development of gastric cancer in patients with normal endoscopic findings

AIM: To investigate the prevalence of H pylori associated corpus-predominant gastritis (CPG) or pangastritis, severe atrophy, and intestinal metaplasia (IM) in patients without any significant abnormal findings during upper-GI endoscopy. METHODS: Gastric biopsies from 3548 patients were obtained during upper GI-endoscopy in a 4-year period. Two biopsies from antrum and corpus were histologically assessed according to the updated Sydney-System. Eight hundred and forty-five patients (mean age 54.8 +/- 2.8 years) with H pylori infection and no peptic ulcer or abnormal gross findings in the stomach were identified and analyzed according to gastritis phenotypes using different scoring systems. RESULTS: The prevalence of severe H pylori associated changes like pangastritis, CPG, IM, and severe atrophy increased with age, reaching a level of 20% in patients of the age group over 45 years. No differences in frequencies between genders were observed. The prevalence of IM had the highest increase, being 4-fold higher at the age of 65 years versus in individuals less than 45 years. CONCLUSION: The prevalence of gastritis featuring at risk for cancer development increases with age. These findings reinforce the necessity for the histological assessment, even in subjects with normal endoscopic appearance. The age-dependent increase in prevalence of severe histopathological changes in gastric mucosa, however, does not allow estimating the individual risk for gastric cancer development--only a proper follow-up can provide this information.     

Causal role of Helicobacter pylori infection in gastric cancer： An Asian enigma

Helicobacter pylori (H pylori) has been etiologically linked to gastric cancer. H pylori infection is more frequent in less developed Asian countries like India, Bangladesh, Pakistan, and Thailand and is acquired at early age than in more developed Asian countries like Japan and China. Frequency of gastric cancer, however, is very low in India, Bangladesh, Pakistan and Thailand compared to that in Japan and China. Similar enigma has been reported from Africa as compared to the West. Seroprevalence of H pylori infection in adult populations of India, Bangladesh, Pakistan and Thailand varies from 55% to 92%. In contrast, seroprevalence of H pylori in Chinese and Japanese adults is 44% and 55%, respectively. Annual incidence rate of gastric cancer in India, Bangladesh, and Thailand is 10.6, 1.3, 7.1 per 100 000 populations, respectively; in contrast, that in China and Japan is 32-59 and 80-115 per 100 000 populations, respectively. Several studies from India failed to show higher frequency of H pylori infection in patients with gastric cancer than controls. Available evidences did not support difference in H pylori strains as an explanation for this enigma. Despite established etiological role of H pylori, situation is somewhat enigmatic in Asian countries because in countries with higher frequency of infection, there is lower rate of gastric cancer. Host's genetic makeup and dietary and environmental factors might explain this enigma. Studies are urgently needed to solve this issue.     

CagA＋ H pylori infection is associated with polarization of T helper cell immune responses in gastric carcinogenesis

AIM:To characterize the immune responses including local and systemic immunity induced by infection with H pylori,especially with CagA+ H pylori strains and the underlying immunopathogenesis. METHODS:A total of 711 patients with different gastric lesions were recruited to determine the presence of H pylori infection and cytotoxin associated protein A (CagA),the presence of T helper (Th) cells and regulatory T (Treg) cells in peripheral blood mononuclear cells (PBMCs),expression of plasma cytokines,and RNA and protein expression of IFN-γ and IL-4 in gastric biopsies and PBMCs were determined by rapid urease test,urea 14C breath test,immunoblotting test,flow cytometry ,real time RT-PCR and immunohistochemistry. RESULTS:Of the patients,629 (88.47%) were infected with H pylori ; 506 (71.16%) with CagA+ and 123 (17.30%) with CagA- strains. Among patients infected with CagA+ H pylori strains,Th1-mediated cellular immunity was associated with earlier stages of gastric carcinogenesis,while Th2-mediated humoral immunity dominated the advanced stages and was negatively associated with an abundance of Treg cells. However,there was no such tendency in Th1/Th2 polarization in patients infected with CagA- H pylori strains and those without H pylori infection. CONCLUSION:Polarization of Th cell immune responses occurs in patients with CagA+ H pyloriinfection,which is associated with the stage and severity of gastric pathology during the progression of gastric carcinogenesis. This finding provides further evidence for a causal role of CagA+ H pylori infection in the immunopathogenesis of gastric cancer.     

Dynamic expression of pepsinogen C in gastric cancer, precancerous lesions and Helicobacter pylori associated gastric diseases

AIM: To investigate the relationship between the expression of pepsinogen C (PGC) and gastric cancer, precancerous diseases, and Helicobacter pylori (H pylori) infection. METHODS: The expression of PGC was determined by immunohistochemistry method in 430 cases of gastric mucosa. H3 Pylori infection was determined by HE staining, PCR and ELISA in 318 specimens. RESULTS: The positive rate of PGC expression in 54 cases of normal gastric mucosa was 100%. The positive rates of PGC expression in superficial gastritis or gastric ulcer or erosion, atrophic gastritis or gastric dysplasia and gastric cancer decreased significantly in sequence (P<0.05; 100%/89.2% vs 14.3%/15.2% vs 2.4%). The over-expression rate of PGC in group of superficial gastritis with H pyloriinfection was higher than that in group without H pylori infection (P<0.05; x2= 0.032 28/33 vs 15/25). The positive rate of PGC expression in group of atrophic gastritis with H pylori infection was lower than that in group without H pylori infection (P<0.01; x2 = 0.003 4/61 vs9/30), and in dysplasia and gastric cancer. CONCLUSION: The level of PGC expression has a close relationship with the degree of malignancy of gastric mucosa and development of gastric lesions. There is a relationship between H pylori infection and expression of antigen PGC in gastric mucosa, the positive rate of PGC expression increases in early stage of gastric lesions with H pylori infection such as gastric inflammation and decreases during the late stage such as precancerous diseases and gastric cancer. PGC-negative cases with H py/ori-positive gastric lesions should be given special attention.     

组织与血清中MG7和胃蛋白酶的表达及对胃癌前病变癌变风险预报的临床意义

目的 通过检测不同类型患者胃黏膜活检组织和血清中MG7和胃蛋白酶(PG)的表达,研究两者的相关性及对胃癌前病变癌变风险预报的临床应用价值.方法 125例中正常胃黏膜12例,浅表性胃炎21例,胃黏膜糜烂溃疡24例,萎缩性胃炎15例,异型增生22例,胃癌31例,采用SP免疫组织化学二步法检测胃黏膜标本中MG7和PGC的表达情况;采用酶联免疫吸附实验检测血清中MG7、PGA和PGC的含量.结果 1.从正常胃黏膜→浅表性胃炎或胃糜烂溃疡→萎缩性胃炎或异型增生→胃癌,组织中MG7表达率依次逐渐上升,差异有统计学意义(P<0.05),血清中MG7含量亦有升高趋势(P<0.01),两者具有良好的相关性(r:0.346,P=0.001).2.从正常胃黏膜→浅表性胃炎或胃糜烂溃疡→萎缩性胃炎或异型增生→胃癌,组织中PGC表达率依次逐渐下降,差异有统计学意义(P<0.05);血清中MG7含量逐渐升高,PGA含量依次降低,但均无统计学意义(P>0.05);各组PGA/PGC比值依次下降,浅表性胃炎组与胃癌组比较差异有极显著意义(P<0.01),与萎缩性胃炎/异型增生组相比差异显著(P<0.05);PGA/PGC的比值随着其病变组织中PGC表达的降低而明显下降(P<0.05),两者具有良好的相关性(r=0.287,P=0.001).结论 1.胃黏膜细胞恶性程度与MG7表达呈正相关而与PGC表达呈负相关,有望将MG7、PGC作为胃癌前病变随访、进行癌变风险预测以及早期癌诊断的预警标志物.2.血清中MG7与组织中MG7表达有良好的相关性,血清中PGA/PGC与组织中PGC表达亦有良好的相关性,以血清为标本代替组织检测具有取材方便、依从性好等优点,便于临床推广应用.     

胃癌及非癌组织中环氧合酶-2和人胃癌相关MG7抗原表达及意义

目的 研究胃癌中环氧合酶-2(COX-2)和人胃癌相关抗原(MG7-Ag)表达的相关性及意义。方法 采用ABC免疫组化法检测l00例藏族胃癌手术患者癌组织及其相应非癌组织和部分远处脏器转移灶中COX-2和MG7-Ag的表达；用甲苯胺蓝染色和改良Giemsa染色法同时检测胃癌组织中幽门螺杆菌(Hp)感染状况。结果胃癌中C0X9-2和MG7-Ag的阳性检出率分别为88．0％和92．0％；在非癌组织中COX-2和MG7-Ag的阳性检出率从慢性浅表性胃炎、慢性萎缩性胃炎、肠上皮化生到不典型增生均呈递增趋势；伴淋巴结和远处脏器转移的胃癌中COX-2的阳性表达率高于无淋巴结转移(P＜0．05)和无远处脏器转移的胃癌组织(P＜0．05)；4l例Hp阳性胃癌组织中COX-2阳性表达率明显高于Hp阴性的胃癌组织(P＜0．05)；COX-2和MG7-Ag在胃癌中的表达呈正相关(r=0．48，P＜0．01)。结论 COX-2与MG7-Ag可能在胃癌的演进过程中起着既独立又相瓦协同的作用。     

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.     

幽门螺杆菌感染者胃粘膜癌前病变与Fas抗原表达的关系

目的研究幽门螺杆菌(Hp)感染后胃粘膜癌前病变中 Fas 抗原表达的情况,了解 Hp 在胃癌发生过程中的作用。方法采用免疫组织化学等方法检测83例经病理证实为慢性胃炎病人胃粘膜上皮细胞中 Fas 抗原的表达情况。结果在浅表性胃炎、萎缩性胃炎、肠化生及异型增生中,Fas 抗原表达率分别为20.00%、36.36%、73.33%、43.75%,Fas 抗原在肠化生中的表达率显著高于浅表性胃炎、萎缩性胃炎及异型增生(P<0.01及P<0.05)。Hp 感染者 Fas 抗原表达率为60.71%,显著高于 Hp 阴性者的22.22%(P<0.01)。在萎缩、肠化生及异型增生等癌前病变中,Hp 感染者与未感染者表达率分别为65.96%及28.57%(P<0.01)。结论 Hp 感染对 Fas 抗原表达有一定的影响,Hp 感染可促进 Fas 抗原表达增加,这可能是 Hp 感染诱导胃粘膜上皮细胞凋亡的机制之一。     

血清胃泌素-17、胃蛋白酶原联合幽门螺杆菌检测在老年人胃癌癌前病变及早期胃癌筛查中的价值

目的 探讨血清胃泌素-17(G-17)、胃蛋白酶原(PG)联合幽门螺杆菌(HP)检测在胃癌癌前病变以及早期胃癌筛查中的价值.方法 选取2015年1月至2019年8月我院收治的因上腹不适就诊而确诊为胃部病变的194例病人作为研究对象,其中≥60岁102例为老年组,＜60岁92例为中青年组.所有病人均经胃镜及病理学检查确诊...     

Expression and significance of Musashi-1 in gastric cancer and precancerous lesions

AIM:To investigate expression of stem cell marker Musashi-1(Msi-1)in relationship to tumorigenesis and progression of intestinal-type gastric cancer(GC).METHODS:Endoscopic biopsy specimens and surgical specimens were obtained,including 54 cases of intestinal-type GC,41 high-grade intraepithelial neoplasia,57low-grade intraepithelial neoplasia,31 intestinal metaplasia,and 36 normal gastric mucosa.Specimens were fixed in 10%paraformaldehyde,conventionally dehydrated,embedded in paraffin,and sliced in 4-μm-thick serial sections.Two-step immunohistochemical staining was used to detect Msi-1 and proliferating cell nuclear antigen(PCNA)expression.Correlation analysis was conducted between Msi-1 and PCNA expression.The relationship between Msi-1 expression and clinicopathological parameters of GC was analyzed statistically.RESULTS:There were significant differences in Msi-1and PCNA expression in different pathological tissues(χ2=15.37,P<0.01;χ2=115.36,P<0.01).Msi-1and PCNA-positive cells were restricted to the isthmus of normal gastric glands.Expression levels of Msi-1and PCNA in intestinal metaplasia were significantly higher than in normal mucosa(U=392.0,P<0.05;U=40.50,P<0.01),whereas there was no significant difference compared to low or high-grade intraepithelial neoplasia.Msi-1 and PCNA expression in intestinaltype GC was higher than in high-grade intraepithelial neoplasia(U=798.0,P<0.05;U=688.0,P<0.01).There was a significantly positive correlation between Msi-1 and PCNA expression(rs=0.20,P<0.01).Msi-1expression in GC tissues was correlated with their lymph node metastasis and tumor node metastasis stage(χ2=12.62,P<0.01;χ2=11.24,P<0.05),but not with depth of invasion and the presence of distant metastasis.CONCLUSION:Msi-1-positive cells may play a key role in the early events of gastric carcinogenesis and may be involved in invasion and metastasis of GC.     

胃癌相关基因在癌前病变中的表达

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目的研究藏、汉族胃癌相关抗原MG