E-cadherin,β-catenin,Cyclin D1在胃腺癌中的表达及临床意义

目的:研究E-cadherin,β-catenin,Cyclin D1在胃腺癌组织中的表达,探讨三者的表达及临床病理意义.方法:采用免疫组织化学SP法检测73例胃腺癌组织及18例正常胃黏膜组织中E-cadherin,β-catenin,Cyclin D1蛋白的表达.结果:正常胃黏膜组织中E-cadherin和β-catenin均呈清晰的棕褐色染色在上皮细胞细胞膜.E-cadherin和β-catenin在胃癌细胞中出现细胞质和/或细胞核异常染色,其异常表达率分别为63.01%(46/73)和56.16%(41/73),且两者的异常表达与胃腺癌的分化程度、TNM分期、浸润深度及淋巴结转移相关,与患者的性别、年龄、肿瘤大小无关.胃腺癌中E-cadherin和β-catenin表达密切相关.Cyclin D1在胃腺癌组织中的阳性表达率为67.12%(49/73),明显高于其在正常胃黏膜组织中的表达(0%,0/18),且与胃腺癌的分化程度和淋巴结转移相关.E-cadherin和β-catenin在胃癌中的异常表达与Cyclin D1的过表达呈显著的正相关(r=0.249,r=0.376,P＜0.05).结论:胃腺癌中存在E-cadherin和β-catenin基因的失活及蛋白表达下调.E-cadherin和β-catenin的异常表达可能通过促使或激活Cyclin D1的过表达而参与胃癌的发生和发展.     

转化生长因子βⅡ型受体在胃癌组织中表达的研究

目的:研究转化生长因子β(TGFβ)Ⅱ型受体在胃癌组织中的表达及其意义.方法:应用免疫组织化学方法,对20例正常胃粘组织及74例胃癌组织(高中分化腺癌32例,低分化腺癌23例,黏液腺癌14例,印戒细胞癌5例)TGFβⅡ型受体的表达情况进行了研究.结果:在正常胃黏膜组织,TGFβⅡ型受体主要表达于腺体的体底部;在胃高中分化腺癌组织中,TGFβⅡ型受体表达减少(P＜0.05,vs正常胃黏膜);在低分化腺癌及黏液印戒细胞癌中,其表达明显减少(P均＜0.01,vs正常胃黏膜).结论:TGFβⅡ型受体表达的减少可能在胃癌的发生发展中起了一定的作用.     

E-cadherin, beta-catenin, Cyclin D1在胃腺癌中的表达及临床意义

目的研究E-cadherin,β-catenin,Cyclin D1在胃腺癌组织中的表达,探讨三者的表达及临床病理意义.方法采用免疫组织化学SP法检测73例胃腺癌组织及18例正常胃黏膜组织中E-cadherin,β-catenin,Cyclin D1蛋白的表达.结果正常胃黏膜组织中E-cadherin和β-catenin均呈清晰的棕褐色染色在上皮细胞细胞膜.E-cadherin和β-catenin在胃癌细胞中出现细胞质和/或细胞核异常染色,其异常表达率分别为63.01%(46/73)和56.16%(41/73),且两者的异常表达与胃腺癌的分化程度、TNM分期、浸润深度及淋巴结转移相关,与患者的性别、年龄、肿瘤大小无关.胃腺癌中E-cadherin和β-catenin表达密切相关.Cyclin D1在胃腺癌组织中的阳性表达率为67.12%(49/73),明显高于其在正常胃黏膜组织中的表达(0%,0/18),且与胃腺癌的分化程度和淋巴结转移相关.E-cadherin和β-catenin在胃癌中的异常表达与Cyclin D1的过表达呈显著的正相关(r=0.249,r=0.376,P＜0.05).结论胃腺癌中存在E-cadherin和β-catenin基因的失活及蛋白表达下调.E-cadherin和β-catenin的异常表达可能通过促使或激活Cyclin D1的过表达而参与胃癌的发生和发展.     

胃癌中血管生成素-2的表达及意义

应用免疫组织化学方法检测55例胃癌组织、12例癌旁胃组织和正常胃组织中的血管生成素-2(Ang-2)蛋白的表达及微血管密度(MVD).发现Ang-2蛋白表达及MVD在胃癌组织中均显著高于癌旁正常组织及正常胃黏膜组织;胃癌中Ang-2表达与浸润深度、淋巴结转移、病理分期、肿瘤分化程度密切相关.认为Ang-2可能在胃癌的发生、发展中起重要作用,有望作为胃癌抗血管治疗的靶点.     

RUNX3、RASSF1A启动子高甲基化与胃癌进展转移的关系

目的:探讨胃癌RUNX3、RASSF1A基因启动子甲基化在胃癌进展转移中的作用及意义.方法:RT-PCR和MSP检测62例胃癌标本及56例正常胃黏膜组织RUNX3、RASSF1A基因mRNA表达及甲基化状况,免疫组织化学检测VEGF在RUNX3、RASSF1A甲基化与非甲基化胃癌组织及20例正常组织中的表达,并分析RUNX3、RASSF1A甲基化与VEGF表达的关系.结果:胃癌组织RUNX3与RASSF1A表达较正常组织均明显降低(0.629±0.461 vs 0.893±0.543,0.653±0.476 vs 0.858±0.581,均P<0.05),且RUNX3与RASSF1A甲基化率均高于正常组织(69.4%VS 26.8%,66.1%vs 23.2%.均P<0.01).胃癌组织中RUNX3、RASSF1A甲基化组mRNA表达量较非甲基化组明显降低(0.545±0.299 vs 0.736±0.291,0.562±0.208 vs 0.674±0.185,均P<0.05).RASSF1A甲基化与肿瘤TNM分期及浸润深度相走RUNX3甲基化与肿瘤淋巴结转移、血管侵犯及TNM分期相关(P<0.05).RUNX3甲基化组胃癌组织VEGF蛋白表达高于非甲基化组(86.0%vs57.9%),RUNX3甲基化与VEGF表达相关(P<0.05).结论:RUNX3、RASSF1A启动子高甲基化可能是导致其表达降低的原因,并与胃癌进展演变相关.RUNX3甲基化可能参与胃癌血管、淋巴管转移.     

SLP-2基因在直肠癌中的表达及意义

目的研究直肠癌组织中SLP-2基因的表达情况。方法应用免疫组化法及RT-PCR法检测40对直肠癌及其癌旁正常直肠组织中SLP-2蛋白及mRNA的表达情况,分析直肠癌病例临床病理特征与SLP-2蛋白表达的关系。结果免疫组化及RT-PCR结果显示SLP-2在直肠癌组织中的表达高于正常配对直肠组织(均P<0.05),且SLP-2蛋白的表达与直肠癌TNM分期及有无淋巴结转移相关(均P<0.05)。结论 SLP-2基因在直肠癌组织中表达升高,可能参与直肠癌的发生发展和转移。     

缺氧诱导因子-2α在胃癌组织中的表达及临床意义

目的:探讨缺氧诱导因子-2α(hypoxia inducible factor-2α, HIF-2α)在胃癌组织中的表达及其临床意义.方法:采用免疫组织化学和逆转录聚合酶链反应检测36例胃癌及正常胃黏膜上皮组织中HIF-2α蛋白及mRNA的表达, 并分析其表达与胃癌临床病理特征的关系.结果:HIF-2α蛋白在胃癌组织中的阳性表达率显著高于正常胃黏膜上皮(83.3% vs 8.3%,P <0.05), 并且其在胃癌组织中的阳性表达率随分化程度的降低而显著增高(P <0.05);在有淋巴结转移组中HIF-2α蛋白的阳性表达率显著高于无淋巴结转移组(91.3% vs 69.2%,P <0.05). HIF-2α mRNA在胃癌组织中的阳性表达率及表达水平均显著高于正常胃黏膜上皮(77.8% vs 5.6%, 0.755±0.238 vs 0.581±0.147, 均P <0.05);HIF-2α mRNA的表达与胃癌患者的分化程度和淋巴结转移均存在明显相关性(均P <0.05).结论:HIF-2α的表达可能与胃癌的发生发展有关, 并对判断胃癌患者的生物学行为具有一定的意义.     

KLF6在胃癌和癌前病变中的表达及其意义

目的:探讨KLF6(krüppel-like factor 6)在胃癌和癌前病变中的表达及其意义.方法:收集郑州大学第二附属医院手术切除32例胃癌组织及其配对的正常胃黏膜组织新鲜标本,采用RT-PCR检测组织中KLF6 mRNA的表达.同期收集20例正常胃黏膜、45例肠上皮化生、16例异型增生及30例胃癌组织存档蜡块,采用免疫组织化学SP法检测组织中KLF6蛋白的表达,并结合临床资料进行分析.结果:正常胃黏膜与Ⅲ型肠上皮化生、异型增生及胃癌组间KLF6蛋白的表达差异有统计学意义(均P<0.05);KLF6蛋白的表达与肿瘤分化程度、肿瘤大小相关,差异有统计学意义(均P<0.05).正常胃黏膜与胃癌组织KLF6 mRNA表达差异无统计学意义(P=0.357).结论:KLF6蛋白的表达异常与Ⅲ型肠化、异型增生、胃癌的发生发展密切相关,其在监测癌前病变的进展及早期胃癌的发现中有一定价值.     

E-选择素蛋白及mRNA在胃腺癌中的表达及其临床意义

目的检测胃腺癌组织中E-选择素蛋白及mRNA的表达及其临床意义。方法应用免疫组化法、逆转录-聚合酶链反应(RT-PCR)技术联合检测90例胃腺癌组织及50例正常胃黏膜组织中E-选择素蛋白及mRNA的表达情况。结果胃腺癌组织E-选择素蛋白及mRNA表达均高于正常胃黏膜组织(P0.05)。E-选择素蛋白及mRNA在胃腺癌组织中的表达均与分化程度、淋巴结转移、浸润深度、TNM分期相关(P0.05),与年龄、性别无关(P0.05)。结论 E-选择素与胃腺癌的发生、发展密切相关,将为评估胃腺癌的浸润、转移潜能和预后提供理论依据。     

胃癌组织中三叶肽因子1的表达与血管形成的关系

目的:研究三叶肽因子1(TFF-1)在人胃癌组织中的表达及其与胃癌血管形成的关系。方法:应用免疫组织化学S-P法检测TFF-1在40例原发性胃癌及10例正常胃黏膜组织中的表达,同时检测微血管密度(MVD,以抗CD 34标记)。结果:10例正常胃黏膜组织TFF-1全部阳性表达,40例胃癌组织TFF-1表达阳性率为40％(16/40)。其阳性表达与胃癌细胞的低分化程度有关(P<0.05),而与患者的性别、肿瘤的浸润程度、淋巴结转移与否无关。胃癌组织MVD明显高于正常胃黏膜组织。TFF-1阳性及阴性表达组MVD均值分别为34.06±6.08、27.96±9.72,两组间MVD均值差异有统计学意义(P<0.05)。结论:胃癌组织中TFF-1常有表达缺失,而其高表达与肿瘤微血管形成、胃癌细胞低分化程度有关。     

Wnt信号通路靶基因GS mRNA及蛋白在胃癌中的表达

目的: 探讨Wnt信号通路的靶基因GS mRNA及蛋白在胃癌中的表达及其临床意义.方法: 荧光实时定量PCR(FQ-PCR)检测52例胃癌组织及癌旁正常组织GS mRNA表达;免疫组织化学技术(SP法)检测97例胃癌组织、30例癌旁正常组织及10例肠化生组织中GS蛋白表达水平差异.结果: 癌组织和癌旁正常组织GS mRNA表达有显著差异(25.508±5.090 vs 13.001±2.040,P<0.05). 癌组织GS蛋白表达与组织学类型、Lauren分型及淋巴结转移密切相关(χ2= 26.994,54.929,5.173,均P<0.05),与肿瘤大小、TNM分期、远处转移及患者的性别和年龄等无明显相关.结论: GS mRNA和蛋白高表达同胃癌生物学行为密切相关,可能与胃癌的发生、发展及预后有关.     

miR-1180在胃癌中的表达及其对胃癌增殖、凋亡的影响

目的研究miR-1180在胃腺癌组织及胃癌细胞系中的表达及其对胃癌细胞增殖、凋亡的影响,探讨miR-1180在胃癌中可能的作用机制。方法应用qRT-PCR检测58例胃腺癌及20例癌旁正常组织中miR-1180的表达,分析其表达与胃腺癌临床病理特征的关系。检测miR-1180在胃癌细胞系中的表达,慢病毒干扰技术下调SGC-7901中miR-1180的表达,检测下调后对SGC-7901增殖、凋亡及细胞周期的影响。结果与癌旁正常组织比较,58例胃腺癌组织中miR-1180的表达明显增加(t=16.463,P=0.000),miR-1180的表达与患者的肿瘤大小、TNM分期及淋巴结转移有关(P均<0.05)。miR-1180在胃癌细胞系中表达升高(P=0.000),下调SGC-7901中miR-1180的表达,可见细胞增殖减少(3113±74 vs 1673±51,P=0.000),凋亡增加(4.313±0.220 vs 7.717±0.125,P=0.000);细胞周期G 1期细胞明显增加(45.89±0.33 vs 60.44±0.390,P=0.000),S期细胞明显减少(35.523±0.354 vs 21.953±0.444,P=0.000),G 2期细胞变化不大(18.587±0.672 vs 17.603±0.731,P=0.162)。结论miR-1180的表达促进胃癌的进展,胃癌中miR-1180的高表达与预后不良有关。     

Expression and significance of CD44s, CD44v6, and nm23 mRNA in human cancer

AIM: To investigate the relationship between the expression levels of nm23 mRNA, CD44s, and CD44v6,and oncogenesis, development and metastasis of human gastric adenocarcinoma, colorectal adenocarcinoma,intraductal carcinoma of breast, and lung cancer.METHODS: Using tissue microarray by immuhistochemical (IHC) staining and in situ hybri-dization (ISH), we examined the expression levels of nm23mRNA, CD44s, and CD44v6 in 62 specimens of human gastric adenocarcinoma and 62 specimens of colorectal adenocarcinoma; the expression of CD44s and CD44v6in 120 specimens of intraductal carcinoma of breast and 20 specimens of normal breast tissue; the expression of nm23 mRNA in 72 specimens of human lung cancer and 23 specimens of normal tissue adjacent to cancer.RESULTS: The expression of nm23 mRNA in the tissues of gastric and colorectal adenocarcinoma was not significantly different from that in the normal tissues adjacent to cancer (P＞0.05), and was not associated with the invasion of tumor and the pathology grade of adenocarcinoma (P＞0.05). However, the expression of nm23 mRNA was correlated negatively to the lymph node metastasis of gastric and colorectal adenocarcinoma (r = -0.49, P＜0.01; r = -4.93, P＜0.01). The expression of CD44s in the tissues of gastric and colorectal adenocarcinoma was significantly different from that in the normal tissues adjacent to cancer (P＜0.05;P＜0.01). CD44v6 was expressed in the tissues of gastric and colorectal adenocarcinoma only, the expression of CD44v6 was significantly associated with the lymph node metastasis, invasion and pathological grade of the tumor (r = 0.47, P＜0.01; r = 5.04, P＜0.01). CD44sand CD44v6 were expressed in intraductal carcinoma of breast, the expression of CD44s and CD44v6 was significantly associated with lymph node metastases and invasion (P＜0.01). However, neither of them was expressed in the normal breast tissue. In addition, the expression of CD44v6 was closely related to the degree of cell differentiation of intraductal carcinoma of breast (x2= 5.68, P＜0.05). The expressional level of nm23mRNA was closely related to the degree of cell differentiation (P＜0.05) and lymph node metastasis (P＜0.01), but the expression of nm23 gene was not related to sex, age, and type of histological classification (P＞0.05).CONCLUSION: Patients with overexpression of CD44s and CD44v6 and low expression of nm23 mRNA have a higher lymph node metastatic rate and invasion. In addition, overexpression of CD44v6 is closely related to the degree of cell differentiation. Detection of the three genes is able to provide a reliable index to evaluate the invasion and metastasis of tumor cells.     

Significance of vascular endothelial growth factor messenger RNA expression in gastric cancer

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Cyr61在胃癌中的表达和意义

背景：Cyr61为CCN家族成员之一,又名CCN1,是一种分泌性蛋白。研究发现Cyr61过表达在多种人类恶性肿瘤的发生、侵袭、转移、复发中发挥重要作用。近年来,Cyr61与胃癌的关系日益受到关注。目的：检测Cyr61在胃癌组织和配对癌旁非癌胃黏膜中的表达并探讨其意义。方法：以RT—PCR检测43例胃癌、40例癌旁非癌胃黏膜标本的Cyr61mRNA表达．以免疫组化方法检测82例胃癌、80例癌旁非癌胃黏膜石蜡包埋组织的Cyr61蛋白表达,分析Cvr61在癌旁非癌胃黏膜和不同浸润深度胃癌组织中的表达差异。结果：胃癌组织Cyr61mRNA相对表达量和Cyr61蛋白高表达率均显著高于癌旁非癌胃黏膜（Cvr61mRNA：0．5286＋0．2139对0．3450＋0．1862,P=0．000;Cyr61蛋白：61．0％对32．5％,P〈0．05）。T。期胃癌组织Cyr61蛋白高表达率显著高于T。。期胃癌组织和癌旁非癌胃黏膜（72．2％对39．3％和32．5％,P〈0．05）,T1-2期胃癌组织与癌旁非癌胃黏膜之间则无明显差异（P〉0．05）。结论：Cyr61在胃癌组织中呈过表达．其表达与胃癌浸润深度相关．提示Cyr61可促进胃癌侵袭,并有望成为预测胃癌预后的分子标记物。     

miR-29对胃腺癌细胞侵袭力的影响

目的探讨miR-29对胃腺癌细胞侵袭力的影响,以期为胃癌的转移、侵袭机制提供线索。方法采用实时荧光定量PCR技术检测46例患者胃腺癌标本及癌旁组织中miR-29表达,分析与患者临床病理特征的关系。结果 PCR反应检测结果显示miR-29a、miR-29b、miR-29c在胃癌组织中相对含量分别为14.13±5.78、9.81±1.95、16.77±2.04,在癌旁组织中分别为31.64±10.26、26.88±5.03、52.57±8.02,胃癌组织中的miR-29相对含量明显低于癌旁组织(P0.05);将胃癌组织标本与癌旁组织标本中的miR-29相对含量计算比值(C/P),患者不同性别、年龄、TNM分期、浸润深度、分化程度时C/P值相比,差异无统计学意义(P0.05);存在淋巴结转移时miR-29a C/P值明显低于无淋巴结转移时(P0.05),存在远处转移时miR-29b、miR-29c C/P值明显低于无远处转移时(P0.05)。结论胃腺癌组织中miR-29表达明显低于癌旁组织,miR-29a在淋巴结转移及miR-29b、miR-29c在远处转移患者胃腺癌组织中表达降低,提示其可能与胃癌的侵袭及转移有关。     

Relationship between matrix metalloproteinase-2 mRNA expression and clinicopathological and urokinase-type plasminogen activator system parameters and prognosis in human gastric cancer

AIM: To investigate the relationship between matrix metalloproteinase-2 (MMP-2) mRNA expression and clinicopathologic and urokinase-type plasminogen activator (uPA) system parameter and prognosis in human gastric cancer. METHODS: Expression of MMP-2 mRNA, uPA, and uPA-R mRNA in tumor tissues and ≥5 cm adjacent normal tissues from 67 cases of gastric cancer was studied using RT-PCR and Northern blot respectively.Survival analyses were done using the Kaplan-Meier method. RESULTS: The expression rates of MMP-2 mRNA,uPA and uPA-R mRNA in tumor tissues (31%,41%,and 51%, respectively) were significantly higher than those in ≥5 cm adjacent tissues (19%, 11%, and 9%; X2=4.59,43.58, and 53.24 respectively, P<0.05,0.0001,and 0.0001, respectively). Expression of MMP-2 mRNA was significantly correlated with lymph node metastasis (metastasis: 61.9%, no metastasis: 39.1%, X2= 7.61, P<0.05),Lauren's classification of diffuse/mixed types:54.2%,intestinal type: 26.3%,X2 = 4.25, P<0.05, expression of uPA and uPA-R mRNA (uPA+: 55.1%, uPA-: 22.2% and uPA-R+: 54.9%, uPA-R-: 18.8%, X2=5.72 and 6.40 respectively, P<0.05).Kaplan-Meier survival analysis of MMP-2 mRNA expression did not show significant difference in all 67 cases, but revealed an association of the expression of MMP-2 mRNA, uPA, and uPA-R mRNA with worse prognosis (P= 0.0083, 0.0160, and 0.0094, respectively). CONCLUSION: MMP-2 may play an important role in the development of invasion and metastasis of gastric cancer.     

Significance of vascular endothelial growth factor expression and its correlation with inducible nitric oxide synthase in gastric cancer

AIM:To investigate the clinical significance of theexpression of VEGF_(165)mRNA and the correlation withvascular endothelial growth factor (VEGF) protein andinducible nitric oxide synthase (iNO) in human gastriccancer.METHODS:We tested VEGF_(165)mRNA expression in 31 casesof resected gastric cancer specimens and normal pairedgastric mucosae by RT-PCR.Total RNA was extracted withTRIzol reagents,transcribed into cDNA with oligo (dT_(15))priming,inner controlled with β-actin expression andagarose gel isolated after PCR.VEGF expression wasquantitated with IS1000 imaging system.Meanwhile wealso examined expression levels of VEGF protein and iNOSin 85 cases of gastric cancer.All paraffin-embeddedsamples were immunohistochemically stained by streptavidin-peroxidase method (SP).RESULTS:The mean expression of VEGF_(165)mRNA ingastric cancer was 1.125±0.356,significantly higher thanthat of normal paired mucosae,which was 0.7604±0.278.The data indicated that the expression level ofVEGF_(165)mRNA was well related to lymph node metastasisand TNM stages of UICC.The expression levels in patientswith lymph node metastasis and without lymph nodemetastasis were 1.219±0.377 and 0.927±0.205 respectively(P<0.05).The expression in stages Ⅰ,Ⅱ,Ⅲ,Ⅳ was0.934±0.194,1.262±0.386 respectively (P<0.01).Furtheranalysis showed the lymph node metastasis rate in thegroup with over-expression of VEGF was higher than thatin the group with low expression of VEGF (83.3% vs 46.2%),and the ratio of stage Ⅲ Ⅳ in the group with over-expression of VEGF was also higher than that in the groupwith low expression with VEGF (77.8% vs 33.8%) (P<0.05).The positive rates of expression of VEGF protein and iNOSin 85 cases of gastric cancer were 75.4% and 58.8%respectively,and 50.1% of the patients showed positivestaining both for iNOS and VEGF,the correlation with thetwo factors was significant (P=0.018).But more intensive analysis showed the immunoreactive grades of VEGF werenot associated with that of iNOS.CONCLUSIONS:The expression of VEGF_(165)mRNA is wellrelated with lymph node metastasis and TNM stages of UlCCin gastric cancer,and is concerned with the invasivenessand metastasis of gastric cancer.The relationship can beobserved between the expression of VEGF and iNOS in gastriccancer.