The Effect of Helicobacter Pylori Infection on Expression of hMSH2, hMLH1 and p53 in Gastric Carcinogenesis

Objective： To detect the expression of hMSH2, hMLH1 and p53 in gastric epithelial cells with and without Helicobactcr pylori （H. pylori） infection and investigate the relationship between H. pylori infection and these genes in gastric carcinogenesis. Methods： H. pylori infection was detected by rapid urease tests. Expression of hMSH2, hMLHland p53 in gastric cancer （GC） tissue, its adjacent mucosa, gastritic mucosa and normal mucosa was assessed by immunohistochemistry SP method. Results： Positive expression rate of hMSH2 in GC tissue （62.7%） was higher than those in adjacent mucosa （29.4%）, gastritic mucosa （32.4%） and normal mucosa （30.0%） （P〈0.001）. Positive rate of hMSH2 in poorly differentiated adenocarcinoma （76.4%） was higher than those in other carcinomas （54.3%, 53.1%） （P〈0.05）. Positive expression rate of hMLH1 in GC tissue （64.3%） mucosa （82.4%） and normal mucosa （80.0%） was lower than those in adjacent mucosa （84.4%）, gastritic （P〈0.01）. Positive rate of hMLH1 in mucoid carcinoma （43.7%） was lower than those in other carcinomas （78.2%, 64.7%） （P〈0.01）. Positive expression rate of p53 in GC tissue （51.9%） was higher than those in adjacent mucosa （3.1%）, gastritic mucosa （0.0%） and normal mucosa （0.0%） （P〈0.001）. Positive rate of p53 in well differentiated adenocarcinoma （32.6%） was lower than those in other carcinomas （58.8%, 68.7%） （P〈0.01）. Positive rates of hMSH2 and hMLH1 in GC with H. pylori infection were lower than those without the infection, respectively （P〈0.05）. Positive rate of p53 in GC with H. pylori infection （61.4%） was higher than that without the infection （40.6%） （P〈0.05）. Conclusion： Gastric carcinogenesis may be associated with abnormal expression of hMSH2, hMLH1 and p53; H. pylori infection affecting expression of these genes may be one of its carcinogenic mechanisms.

The Effect of Helicobacter pylori Infection on hMSH2 and P53 Proteins in Gastric Carcinogenesis

OBJECTIVE To investigate the effect of Helicobacter pylori （H pylon） infection on expression of hMSH2 and P53 and its possible carcinogenic mechanism. METHODS H pylori infection was detected using a rapid urease test and haematoxylin and eosin （H＆E） staining. The hMSH2 and P53 proteins in gastric cancer （GC） tissue, its adjacent mucosa, gastritic mucosa and normal gastric mucosa were detected by the immunohistochemical SP method. RESULTS （1） The positive rate of hMSH2 expression in GC tissue （62.7%）was higher than those in non-cancer tissues （P〈0.001）; the positive rate of hMSH2 expression in poorly differentiated adenocarcinoma （76.4%） was higher than that in other carcinomas （P〈0.05）. The positive rate of P53 expression in GC tissue （51.9%） was higher than that in noncancer tissues （P〈0.001）; the positive rate of P53 expression in well-differentiated adenocarcinoma （32.6 %） was lower than that in other carcinomas （P〈0.01）. （2） The positive rate of hMSH2 expression in GC tissue with H pylori infection was lower than that without the infection （52.8% vs. 74.5%; P〈0.05）. The positive rate of P53 expression in GC tissue with H pylori infection was higher than that without the infection （61.4% vs. 40.6%; P〈0.05）.（3） The expression of hMSH2 and P53 in GC tissue correlated positively （r=0.457, P〈0.01）. CONCLUSION High expression of hMSH2 and P53 as well as their interaction may be involved in gastric carcinogenesis; H pylori infection affecting expression of hMSH2 and P53 may be one of its carcinogenic mechanisms.

The Role of Expression of Mismatch Repair Proteins hMSH2 and hMLH1 in Gastric Carcinogenesis and Its Clinical Significance

OBJECTIVE To investigate the expression of the mismatch repair proteins hMSH2 and hMLH1, and to examine the clinical significance of the intracellular expression site （ICES） in gastric carcinogenesis. METHODS Specimens from 172 cases of gastric cancer, 151 tissues from paraneoplastic gastric mucosa and 34 from noncancerous gastric mucosa were collected in Dalain, China. An immunohistochemical method was used to determine the expression of the hMSH2, hMLH1 proteins and their ICES in the gastric mucosas. RESULTS The rate of hMSH2 expression in gastric cancers, paraneoplastic gastric mucosas and noncancerous gastric mucosas were respectively 69.8%, 49.7% and 32.4%. The rate was significantly higher in gastric cancer compared to the latter two groups （P=0.000）, but there was no obvious difference in the expression between the two latter groups （P=0.067）. The hMLH1 protein expression rates were respectively 73.3%, 57.6% and 41.2% in the above three groups. The expression was significantly higher in the gastric cancer group compared to the two latter groups （P=0.000）, while there was no significant difference between the latter groups （P=0.082）. There was no obvious correlation between the hMSH2 and hMLH1 protein expression rates and related factors, such as gender, age and differentiated level of gastric cancer etc. The cell-nuclear expression of the hMSH2 protein was respectively 70.0%, 58.7% and 36.4% in the gastric cancer, paraneoplastic gastric mucosa and noncancerous gastric mucosa groups. The cytoplasmic expression rates were 30.0%, 41.3% and 63.6% in the three groups. The cell-nuclear expression rate of the hMSH2 protein gradually decreased in the gastric mucosas in the following order： cancer, paraneoplastic and noncancerous but cytoplasmic expression only increased slightly in these groups （r=0.161, P=0.020）. There was no significant difference in the ICES of the hMLH1 protein among the three different gastric mucosas （P=0.659）. CONCLUSION Simultaneous determination of the expression and ICES of the mismatch repair proteins hMSH2 and hMLH1 in the gastric mucosa may be helpful in detecting early gastric cancer.

Identification of hub genes associated with Helicobacter pylori infection and type 2 diabetes mellitus:A pilot bioinformatics study

BACKGROUND Helicobacter pylori(H.pylori)infection is related to various extragastric diseases including type 2 diabetes mellitus(T2DM).However,the possible mechanisms connecting H.pylori infection and T2DM remain unknown.AIM To explore potential molecular connections between H.pylori infection and T2DM.METHODS We extracted gene expression arrays from three online datasets(GSE60427,GSE27411 and GSE115601).Differentially expressed genes(DEGs)commonly present in patients with H.pylori infection and T2DM were identified.Hub genes were validated using human gastric biopsy samples.Correlations between hub genes and immune cell infiltration,miRNAs,and transcription factors(TFs)were further analyzed.RESULTS A total of 67 DEGs were commonly presented in patients with H.pylori infection and T2DM.Five significantly upregulated hub genes,including TLR4,ITGAM,C5AR1,FCER1G,and FCGR2A,were finally identified,all of which are closely related to immune cell infiltration.The gene-miRNA analysis detected 13 miRNAs with at least two gene cross-links.TF-gene interaction networks showed that TLR4 was coregulated by 26 TFs,the largest number of TFs among the 5 hub genes.CONCLUSION We identified five hub genes that may have molecular connections between H.pylori infection and T2DM.This study provides new insights into the pathogenesis of H.pylori-induced onset of T2DM.

miR-155、hMSH2在肾癌进展和预后的作用

通过生物信息学的手段分析miR-155、hMSH2表达情况和肾癌临床数据的相关性,进而阐明两者的关系。材料和方法 应用UALCAN数据库对miR-155、hMSH2进行差异性分析,进一步应用UALCAN数据库分析miR-155、hMSH2和肾癌淋巴转移、临床分级的关系,并应用UALCAN数据库进行蛋白表达验证。结果 miR-155在肾癌组织中的MRNA表达高于正常组织,而hMSH2在肾癌组织中的蛋白表达高于正常组织。结论 miR-155、hMSH2参与了肾癌的发生发展。

Regulatory potential of soil available carbon,nitrogen,and functional genes on N_(2)O emissions in two upland plantation systems

Dynamic nitrification and denitrification processes are affected by changes in soil redox conditions,and they play a vital role in regulating soil N_(2)O emissions in rice-based cultivation.It is imperative to understand the influences of different upland crop planting systems on soil N_(2)O emissions.In this study,we focused on two representative rotation systems in Central China:rapeseed–rice(RR)and wheat–rice(WR).We examined the biotic and abiotic processes underlying the impacts of these upland plantings on soil N_(2)O emissions.The results revealed that during the rapeseed-cultivated seasons in the RR rotation system,the average N_(2)O emissions were 1.24±0.20 and 0.81±0.11 kg N ha^(–1)for the first and second seasons,respectively.These values were comparable to the N_(2)O emissions observed during the first and second wheat-cultivated seasons in the WR rotation system(0.98±0.25 and 0.70±0.04 kg N ha^(–1),respectively).This suggests that upland cultivation has minimal impacts on soil N_(2)O emissions in the two rotation systems.Strong positive correlations were found between N_(2)O fluxes and soil ammonium(NH_(4)^(+)),nitrate(NO_(3)^(–)),microbial biomass nitrogen(MBN),and the ratio of soil dissolved organic carbon(DOC)to NO_(3)^(–)in both RR and WR rotation systems.Moreover,the presence of the AOA-amoA and nirK genes were positively associated with soil N_(2)O fluxes in the RR and WR systems,respectively.This implies that these genes may have different potential roles in facilitating microbial N_(2)O production in various upland plantation models.By using a structural equation model,we found that soil moisture,mineral N,MBN,and the AOA-amoA gene accounted for over 50%of the effects on N_(2)O emissions in the RR rotation system.In the WR rotation system,soil moisture,mineral N,MBN,and the AOA-amoA and nirK genes had a combined impact of over 70%on N_(2)O emissions.These findings demonstrate the interactive effects of functional genes and soil factors,including soil physical characteristics,available carbon and nitrogen,and their ratio,on soil N_(2)O emissions during upland cultivation seasons under rice-upland rotations.

胃癌细胞错配修复基因hMSH2蛋白的表达特点

[目的]探讨错配修复基因hMSH2蛋白在胃癌细胞中的表达特点及意义。[方法]免疫组织化学SP法检测138例胃癌标本hMSH2基因的表达情况。[结果]胃癌hMSH2蛋白表达强度及表达部位均与胃癌分化程度无显著相关关系(P >0 .0 5 ) ;hMSH2蛋白表达强度在核表达及核、浆同时表达者明显强于浆表达者(P <0 .0 5 )。[结论]hMSH2蛋白不能有效地进入核内发挥作用可能是导致错配修复功能下降的另一原因。

胃癌中hMSH2、PTEN和PCNA表达的相关性及意义

目的：探讨胃癌中错配修复基因 hMSH2与 PTEN、PCNA 表达的关系及意义。方法：采用免疫组织化学 SP 法检测胃癌、癌旁和胃炎粘膜中 hMSH2、PTEN 和 PCNA 的表达。结果：(1)hMSH2和 PCNA 在癌组织的表达阳性率均显著高于非癌组织；PTEN 在癌组织的表达阳性率显著低于非癌组织。(2)PTEN 在低分化癌和有淋巴结转移的病例表达阳性率显著低于高分化癌和无转移者。PCNA 在低分化癌和有淋巴结转移的病例表达阳性率显著高于高分化癌和无转移者。(3)hMSH2与 PCNA 蛋白表达呈显著性正相关；PTEN 与 PCNA 蛋白表达呈显著性负相关。结论：hMSH2的高表达及 hMSH2与 PCNA 表达的相互影响与胃癌的发生可能有关；检测3种蛋白有助于判断胃癌的恶性程度和生物学行为。

食管鳞状细胞癌癌组织中hMLH1、hMSH2的表达及其意义

目的:探讨错配修复基因hMSH2、hMLH1在食管鳞癌组织中的表达及其临床意义。方法:采用sP免疫组化的方法检测144例食管鳞癌手术切除标本、30例正常粘膜组织中hMSH2、hMLH1表达情况,并与临床病理参数作相关分析。结果:食管鳞癌组织hMSH2、hMLH1基因阳性表达明显下降,与正常食道粘膜相比相差显著(P<0.01),hMSH2、hMLH1表达缺失与年龄、性别、肿瘤大小、淋巴结转移、浸润深度无显著相关,与肿瘤的分化程度有关(P<0.01)。结论:提示hMLH1和hMSH2基因突变所致的蛋白表达异常缺失与食管鳞状细胞癌发生有关,可能为一种早期事件。

错配修复蛋白hMSH2 hMLH1表达在胃癌发生中的作用及临床意义

目的:探讨错配修复蛋白hMSH2、hMLH1表达及其在细胞内表达位置对胃癌发生的影响及临床意义。方法:收集大连医科大学附属第一医院胃癌标本172例、癌旁胃粘膜标本151例,非癌患者胃粘膜标本34例,应用免疫组织化学方法检测每例胃粘膜标本hMSH2、hMLH1蛋白的表达情况(包括其在细胞内表达位置),应用χ2检验,Spearman等级相关分析在SPSS13.0统计软件上作相关统计。结果:胃癌、癌旁胃粘膜和非癌患者胃粘膜hMSH2蛋白表达率分别为69.8%(120/172)、49.7%(75/151)和32.4%(11/34),胃癌组显著高于后两组(P=0.000),而后两组间无显著性差异(P=0.067);hMLH1蛋白表达率分别为73.3%(126/172)、57.6%(87/151)和41.2%(14/34),胃癌组显著高于后两组(P=0.000),而后两组间无显著性差异(P=0.082)。hMSH2和hMLH1蛋白表达率与胃癌患者的性别、年龄及胃癌分化程度均无显著相关关系。胃癌、癌旁胃粘膜和非癌患者胃粘膜hMSH2蛋白细胞核表达率分别为70.0%(84/120)、58.7%(44/75)和36.4%(4/11),细胞浆表达率分别为30.0%(36/120)、41.3%(31/75)和63.6%(7/11);胃癌、癌旁胃粘膜、非癌患者胃粘膜中,hMSH2蛋白细胞核表达率逐渐降低,而细胞浆表达率则逐渐增高(r=0.161,P=0.020)。三种不同胃粘膜间,hMLH1蛋白在细胞内表达位置无显著性差异(P=0.878)。结论:同时检测胃粘膜错配修复蛋白hMSH2和hMLH1的表达及其细胞内表达位置可能有助于胃癌的早期预警。

错配修复基因hMSH2和hMLH1在胃癌组织中的表达及其与幽门螺杆菌感染的关系

背景与目的:胃癌是一种多因素相关疾病,幽门螺杆菌(Helicobactorpylori,HP)感染是导致胃癌发生的原因之一,但其分子机制不明。错配修复基因是保证DNA复制高保真度的重要基因,与消化道肿瘤发生具有密切关系。本研究通过检测HP感染和非感染胃癌组织及癌旁粘膜组织和慢性浅表性胃炎粘膜组织中错配修复基因hMSH2和hMLH1蛋白的表达,探讨hMSH2、hMLH1基因在胃癌发生中的作用和HP致癌的可能机制。方法:采用尿素酶快速检验法对HP感染情况进行检测;利用免疫组化方法检测胃癌及癌旁粘膜和胃炎粘膜组织中hMSH2和hMLH1的表达情况,采用χ2检验对数据进行统计学分析。结果:hMSH2在胃癌组织中的阳性率(67.1%),显著高于癌旁粘膜组织(35.5%)和胃炎粘膜组织(42.1%)(P<0.05),而后两者无显著性差异(P>0.05)。癌组织中低分化腺癌的hMSH2阳性率(81.1%)显著高于高中分化腺癌(54.5%)和粘液癌(52.9%)(P<0.05);后两者间无显著性差异(P>0.05)。hMLH1的阳性率在胃癌组织(81.6%)、癌旁粘膜组织(90.8%)和胃炎组织(89.5%)间无显著性差异(P>0.05)。hMLH1在粘液癌中的阳性率(47.1%)显著低于高中分化腺癌(81.8%)和低分化腺癌(97.3%)(P<0.05),而后两者间无显著性差异(P>0.05)。在HP感染和非感染胃癌组织中,hMSH2的阳性率分别为56.8%和81.3%,

X射线照射诱导鼻咽癌细胞hMSH2的表达

目的研究X射线照射对鼻咽癌CNE-1细胞错配修复基因hMSH2表达的影响,探讨放射损伤后肿瘤细胞的DNA修复机制。方法应用逆转录-PCR(RT-PCR)、免疫细胞化学及蛋白免疫印迹(Western blot)方法,检测X射线照射后对照组和实验组(照射总剂量分别为0Gy和10Gy)细胞中hM-SH2基因mRNA及蛋白表达。结果实验组细胞hMSH2基因mRNA及蛋白表达在照射终止后逐渐上调,其表达较对照组显著增强(P<0.01)。结论X射线照射可诱导鼻咽癌细胞hMSH2的表达,有助于放射损伤后肿瘤细胞DNA修复,这可能是肿瘤放疗敏感性降低的原因之一。

胃癌中hMSH2、p53和PCNA表达的相关性及意义

目的:探讨胃癌中hMSH2、p53和PCNA表达的相关性及意义。方法:采用免疫组织化学SP法,检测胃癌、癌旁和胃炎粘膜中hMSH2、p53和PCNA表达情况。结果:1)3种基因产物在胃癌中的阳性率均显著高于非癌组织,其中,p53和PCNA在低分化癌中的阳性率显著高于高分化癌,有淋巴结转移者显著高于无转移者(P<0.05)。2)胃癌中hMSH2/PCNA及p53/PCNA表达均呈正相关(P<0.05)。结论:hMSH2、p53和PCNA的异常表达及hMSH2与PCNA之间的相互调节可能与胃癌的发生发展密切相关。

食管癌组织中hMSH2基因的表达

目的观察食管癌组织中DNA错配修复基因hMSH2的表达。方法32例食管癌患者术前均未接受放疗、化疗等其他治疗,标本切除后0.5 h内在癌灶、癌旁及正常残端各取1 cm×1 cm×1 cm大小的组织块,应用原位杂交法检测hMSH2。结果食管癌组织中hMSH2的阳性表达率为46.88%、癌旁为53.12%、正常组织为84.38%。与正常食管组织相比,食管癌和癌旁组织中hMSH2的阳性表达率均明显降低(P<0.05)。hMSH2阳性表达率与食管癌患者年龄及性别,肿瘤大小、肿瘤位置、病理类型、组织学分级、淋巴结转移、浸润深度等均无明显相关性(P>0.05)。结论hMSH2缺失是食管癌发生的早期事件。

Pathogenesis of chronic enteropathy associated with the SLCO2A1 gene:Hypotheses and conundrums

Chronic enteropathy associated with the SLCO2A1 gene(CEAS)is a complex gastroenterological condition characterized by multiple ulcers in the small intestine with chronic bleeding and protein loss.This review explores the potential mechanisms underlying the pathogenesis of CEAS,focusing on the role of SLCO2A1-encoded prostaglandin transporter OATP2A1 and its impact on prostaglandin E2(PGE2)levels.Studies have suggested that elevated PGE2 levels contribute to mucosal damage,inflammation,and disruption of the intestinal barrier.The effects of PGE2 on macrophage activation and Maxi-Cl channel functionality,as well as its interaction with nonsteroidal anti-inflammatory drugs play crucial roles in the progression of CEAS.Understanding the balance between its protective and pro-inflammatory effects and the complex interactions within the gastrointestinal tract can shed light on potential therapeutic targets for CEAS and guide the development of novel,targeted therapies.

错配修复基因hMLH1和hMSH2在胃癌组织中的表达及意义

目的:探讨错配修复基因hMLH1和hMSH2在胃癌发生中的作用.方法:收集青岛大学医学院附属医院普外科手术切除的胃癌组织40例,经病理诊断腺癌33例,黏液腺癌7例,患者术前均未接受放化疗和免疫治疗,每例均取相应癌旁组织.胃镜活检20例慢性胃炎黏膜组织(慢性浅表性胃炎10例,慢性萎缩性胃炎10例).采用Western blot法检测hMLH1和hMSH2蛋白在胃癌组织、癌旁组织及胃炎组织中的表达.结果:胃癌组织中hMSH2蛋白的表达显著高于癌旁组织和胃炎组织(0.28±0.10vs0.23±0.07,0.11±0.10,均P<0.01);hMLH1蛋白在胃炎组织和癌旁组织中的表达显著高于胃癌组织(0.28±0.07,0.26±0.06vs0.22±0.06,均P<0.01);hMLH1和hMSH2在胃癌中的表达与年龄、性别、肿瘤部位、肿瘤大小、浸润深度、组织学类型、分化程度、淋巴结转移、远处转移等无关,差异均无显著性.结论:hMSH2高表达可能是胃癌发生的标志之一,而hMLH1则可能是胃癌预警组织的一种标志物.

散发性结直肠癌hMLH1和hMSH2蛋白表达

目的 研究hMLH1及hMSH2两种错配修复 (mismatchrepair,MMR)蛋白在散发性结直肠癌中的表达变化并评估其可能的临床意义。方法 应用EnVision免疫组化两步法检测 1 1 1例散发性结直肠癌中hMLH1和hMSH2的蛋白表达变化 ,采用Kaplan Meier曲线、Log rank检验分析hMLH1蛋白表达变化与患者生存率之间的关系。 结果 1 1 1例散发性结直肠癌中 ,hMLH1失表达有 1 9例 ,占 1 7 1 % (1 9/ 1 1 1 ) ,hMSH2失表达有 2例 ,占 1 8% (2 / 1 1 1 ) ,两者之和占总散发性结直肠癌病例的 1 8 9% (2 1 / 1 1 1 )。hMLH1或hMSH2蛋白失表达与患者肿瘤部位、组织学类型密切相关。近端结肠、低 -未分化腺癌及黏液腺癌中MMR异常表达比例高 (P <0 0 5 ) ,而与患者年龄、性别、肿瘤大体类型、肿块大小、浸润深度、淋巴结转移与否以及患者的Dukes分期均无显著性相关 (P >0 0 5 )。癌组织中hMLH1正常表达及失表达患者的 5年生存率分别为 6 9 5 7%及73 6 8% ,8年生存率分别为 5 3 5 8%及 73 6 8% ,8年生存率差别较明显 ,然差别无统计学显著性 (P >0 0 5 )。结论 一定比例的散发性结直肠癌中存在MMR基因的缺陷 ,其中hMLH1所起的作用远远大于hMSH2 。

家族史阳性食管癌组织中hMSH2和PTEN蛋白的表达

目的:探讨家族史阳性和阴性食管癌患者癌组织中hMSH2和PTEN蛋白的表达变化与食管癌遗传易感性的关系。方法:采用免疫组化ABC法检测河南省食管癌高发区64例食管癌患者(家族史阳性31例)手术切除标本癌组织、癌旁组织中hMSH2和PTEN蛋白表达情况。结果:家族史阳性食管癌患者hMSH2蛋白阳性表达率为55%(17/31),低于家族史阴性患者的82%(27/33)(P<0.05)。家族史阳性和阴性患者PTEN蛋白阳性表达率分别为42%(13/31)和21%(7/33),差异无统计学意义(P>0.05)。结论:hMSH2表达异常与食管癌高易感性密切相关,而PTEN蛋白表达与食管癌遗传易感性无相关性。

中国人HNPCC家系中hMSH2基因新突变及其功能分析

目的:报道1个在中国人遗传性非息肉病性结直肠癌(HNPCC)家系中发现的基因突变,并对其功能进行分析。方法:抽提1组符合Amsterdam标准的HNPCC家系先证者和其他家系成员的基因组DNA,PCR扩增先证者hMLH119个外显子和hMSH216个外显子,利用变性高效液相技术(dHPLC)筛查,对异常峰型利用DNA测序方法检测基因突变。发现先证者hMSH2基因存在错义突变后,对家系中其他成员和50名散发性大肠癌患者和100名正常成年人进行相同位点的检测,以判定是单核苷酸多态性位点(SNP)还是突变。利用5对微卫星标记对该家系中的2例肿瘤进行微卫星不稳定分析,免疫组化检测蛋白表达,利用同源建模方法对发现的突变位点进行功能分析,以研究突变的病理意义。结果:在该家系的2例结肠癌患者中均发现hMSH2基因第13外显子2108位出现CA的错义突变,导致703位Ser变异为Tyr,即C.2108C>A(p.Ser703Tyr),微卫星结果显示2例肿瘤均为微卫星高度不稳定(MSIH),肿瘤免疫组化结果显示hMSH1基因表达正常而hMSH2基因不表达。同源建模发现该位点与目前报道的hMSH2基因突变不同,突变位于第Ⅳ结构域,Ser突变为Tyr后空间位阻增大,影响了蛋白的正常折叠和功能。结论:Ser703Tyr是中国人HNPCC的一个新的病理性突变。