巨噬细胞抑制因子-1 mRNA在胃癌及癌前病变黏膜组织中的表达及其临床意义

目的 研究巨噬细胞抑制因子-1(MIC-1)mRNA在胃癌及胃癌前病变黏膜组织的表达,及其与临床病理特征间的关系.方法 采用半定量RT-PCR法检测MIC-1 mRNA在58例胃癌组织、30例对应的癌旁组织、19例胃癌前病变黏膜组织和8例胃慢性炎性反应黏膜组织的表达;对比分析其与胃癌临床病理特征的关系.结果 ①MIC-1 mRNA在胃癌中的表达阳性率和相对表达量分别为91.4%和0.751±0.222,均显著高于癌旁5 cm内组织(60.0%和0.546±0.287)和癌旁10 cm外组织(43.3%和0.481±0.209),P值均＜0.01.而癌旁5 cm内及癌旁10 cm外组织表达阳性率和相对表达量间差异无统计学意义(P＞0.05).②胃癌组织中MIC-1 mRNA的表达与肿瘤临床分期、侵袭深度,淋巴结转移及有无远处转移有关(P值均＜0.05),与患者性别,年龄、肿瘤分化程度、肿瘤直径无关(P值均＞0.05).③MIC-1 mRNA在胃癌组织的表达阳性率和相对表达量为91.4%和0.751±0.222,显著高于胃癌前病变黏膜组织(52.6%和0.528±0.077,P＜0.01).胃慢性炎症黏膜组织无表达.结论 MIC-1可能在胃癌的发生发展、侵袭和转移过程中起重要的作用.     

BRMS1基因在胃癌中的表达及意义

目的观察乳腺癌转移抑制基因（BRMS1）在胃癌组织中的表达,并探讨其在胃癌侵袭转移中的作用及与胃癌生物学的关系。方法采用RT-PCR方法检测44例胃癌及相应癌旁正常胃组织中BRMS1的表达。结果 44例胃癌旁正常胃组织中有35例（79.5%）表达BRMS1,而胃癌组织中有14例（31.8%）表达,胃癌组织中BRMS1的表达水平明显低于癌旁正常胃组织（P〈0.01）,BRMS1的表达水平与胃癌的分化程度、浸润程度及淋巴结转移密切相关（P均〈0.05）。结论 BRMS1 mRNA在胃癌组织中表达降低,其可作为反映胃癌浸润、转移潜能的参考指标之一。     

胃癌组织中EGFR和COX-2表达的意义及其相关性

目的:探讨表皮生长因子受体(EGFR)和环氧化酶-2(COX-2)的表达与胃癌侵袭、转移因素的关系以及EGFR与COX-2在胃癌组织中表达的相关性.方法:用免疫组化的方法检测61例胃癌组织和相应的20例癌旁组织石蜡切片中EGFR、COX-2表达情况:用Western blot方法检测10例胃癌组织和相应的癌旁组织中EGFR、COX-2蛋白的表达.结果:免疫组化检测胃癌组织中EGFR及COX-2的阳性表达率分别为36.07%、59.02%均明显高于癌旁组织的0%、25%(χ~2=9.903,P<0.01;χ~2=6.972,P<0.01);COX-2表达与浸润深度、淋巴结转移、TNM分期和病理分化程度有关(χ~2=6.333,P<0.05;χ~2=5.588,P<0.05;χ~2=8.826,P<0.01;χ~2=5.653,P<0.05).EGFR表达与淋巴结转移和TNM分期有关(χ~2 =10.648,P<0.01;χ~2=4.150,P<0.05).EGFR与COX-2表达呈明显相关(r=0.316,P<0.05).Western blot方法检测胃癌组织中EGFR及COX-2的蛋白表达高于癌旁组织(35.89±12.50 vs 15.14±2.15,P<0.01;51.29±23.42 vs 27.65±7.42,P<0.05).结论:EGFR、COX-2在胃癌组织中高表达,EGFR、COX-2的表达与胃癌的侵袭、转移密切有关,COX-2表达与EGFR显著相关.     

血红素氧合酶-1在胃癌腹膜转移中的表达及意义

目的 探讨血红素氧合酶-1(hemeoxygenase-1,HO-1)在胃腺癌及腹膜转移灶、细胞系及耐药细胞系中的表达及意义.方法 用免疫组化法检测68例胄腺癌组织及其腹膜转移灶、转移灶旁无瘤腹膜组织中HO-1的表达,以及46例无腹膜转移的胃腺癌组织中HO-1的表达.Western印迹法检测胃腺癌腹膜转移组织及耐药细胞系HO-1的表达.结果 胃腺癌及其腹膜转移灶HO-1的阳性表达率分别为39.7%(27/68)和41.2%(28/68),显著高于癌旁无瘤腹膜组织[0%(0/68),P<0.01],亦显著高于无腹膜转移胃癌组织[21.7%(10/46),P<0.05].低分化转移灶HO-1表达水平显著高于中、高分化转移灶(P<0.05).Western印迹法检测胃癌腹膜转移患者的转移灶HO-1表达水平显著高于其癌旁无瘤腹膜组织(P<0.05).HO-1在耐药细胞系GC9811-P的表达水平较其亲本细胞系明显上调(P<0.05).结论 HO-1在胃腺癌腹膜转移过程中表达增高,HO-1可能参与胃癌腹膜转移发生.高表达HO-1与胃癌腹膜转移组织的恶性程度有关,其信号转导通路可能存在于组织的上皮细胞,并可能与多药耐药有关.     

SLP-2在胃癌中的表达及意义

目的:研究SLP-2基因在胃腺癌及正常胃黏膜中的表达情况.方法:应用免疫组织化学法及RT-PCR法分别检测45例及40例胃腺癌及其癌旁正常胃黏膜中SLP-2基因的表达,并结合免疫组织化学结果及胃癌患者的临床病理资料进行分析.结果:免疫组织化学和RT-PCR结果均显示SLP-2在胃腺癌组织中的表达高于正常配对胃黏膜(68.9%vs26.7%,1.12±0.47vs0.63±0.31,均P<0.01),且SLP-2的表达与胃癌TNM分期及有无淋巴结转移相关(2=5.32、4.78,均P<0.05).结论:SLP-2基因在胃腺癌组织中高表达,可能参与胃腺癌的发生发展和转移.     

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.     

Livin、Smac/DIABLO和PTEN在胃癌组织中的表达及其与胃癌的相关性

目的:探讨凋亡抑制蛋白Livin及线粒体促凋亡蛋白Smac/DIABLO和PTEN在胃癌发生发展分子机制中的调控作用及意义.方法:实时荧光定量PCR检测75例手术切除胃癌患者组织, 20例癌旁组织及20例正常胃组织中Livin mRNA和Smac/DIABLO mRNA的表达, Western blot结合免疫组织化学法检测两者与PTEN蛋白的表达及组织学定位.结果:正常胃组织及癌旁组织中均无Livin mRNA表达, 胃癌组织中Livin mRNA相对表达量显著上调(6.374±4.759), 其表达在低分化胃癌组及淋巴结转移组具有显著差异(χ2 = 9.60, 5.51, P<0.01或0.05), 与肿瘤大小, 浸润程度及TNM分期等病理表现无关;Smac/DIABLO mRNA胃癌组织中的表达水平低于正常胃组织及癌旁组织, 但差异无显著性(0.731±0.420 vs 1.104±0.276, 1.061±0.737, 均P>0.05), Smac/DIABLO mRNA的表达水平与胃癌各临床病理因素无关; 其蛋白表达量与Smac/DIABLO mRNA的表达水平存在差异. Smac/DIABLO在肠型胃癌与弥漫型胃癌中的表达有显著差异(χ2 = 5.06,P<0.05). 正常胃黏膜及胃癌组织中未检出PTEN蛋白表达.结论:Li v i n、Sma c/DIABLO及PTEN的表达水平在不同阶段及病理类型的胃癌中存在差异. 实时荧光定量PCR检测Li v i n及Smac/DIABLO的表达量, 有可能为判断胃癌的发生, 分化程度及预测化疗敏感性提供新的指标.     

荧光定量PCR检测非小细胞肺癌中MTA1和E-cadherin的表达及意义

目的探讨肿瘤转移相关蛋白家族1(MTA1)和E-钙黏蛋白(E-cadherin)在人非小细胞肺癌(NSCLC)中的表达及意义。方法采用实时荧光定量PCR(Q-PCR)联合检测40例NSCLC组织、12例癌旁组织、12例良性病变肺组织中MTA1和E-cadherin mRNA表达的相对水平,分析他们的表达与临床组织病理学特征的关系。结果MTA1 mRNA在NSCLC中平均表达水平高于癌旁和良性疾病组织(P<0.05);E-cadherin mRNA在NSCLC中平均表达水平低于癌旁和良性疾病组织(P<0.05);在NSCLC中MTA1和E-cadherin的表达呈负相关(r=-0.561,P<0.05);在癌旁组织和良性疾病组织中MTA1和E-cadherin的表达无统计学差异(P>0.05);MTA1和E-cadherinmRNA表达水平与淋巴结转移及临床分期有关(P<0.05)。结论 MTA1过度表达及E-cadherin表达的下调或缺失与NSCLC浸润和转移呈正相关,联合检测NSCLC中MTA1和E-cadherin的表达,可用于预后评估。     

血红素氧合酶-1在胃癌腹膜转移中的表达及意义

目的 探讨血红素氧合酶-1(hemeoxygenase-1,HO-1)在胃腺癌及腹膜转移灶、细胞系及耐药细胞系中的表达及意义.方法 用免疫组化法检测68例胄腺癌组织及其腹膜转移灶、转移灶旁无瘤腹膜组织中HO-1的表达,以及46例无腹膜转移的胃腺癌组织中HO-1的表达.Western印迹法检测胃腺癌腹膜转移组织及耐药细胞系HO-1的表达.结果 胃腺癌及其腹膜转移灶HO-1的阳性表达率分别为39.7%(27/68)和41.2%(28/68),显著高于癌旁无瘤腹膜组织[0%(0/68),P<0.01],亦显著高于无腹膜转移胃癌组织[21.7%(10/46),P<0.05].低分化转移灶HO-1表达水平显著高于中、高分化转移灶(P<0.05).Western印迹法检测胃癌腹膜转移患者的转移灶HO-1表达水平显著高于其癌旁无瘤腹膜组织(P<0.05).HO-1在耐药细胞系GC9811-P的表达水平较其亲本细胞系明显上调(P<0.05).结论 HO-1在胃腺癌腹膜转移过程中表达增高,HO-1可能参与胃癌腹膜转移发生.高表达HO-1与胃癌腹膜转移组织的恶性程度有关,其信号转导通路可能存在于组织的上皮细胞,并可能与多药耐药有关.     

MTA1蛋白在胃癌中的表达及临床意义

应用免疫组化SP法检测67例胃癌、31例癌旁非典型增生及20例正常胃黏膜组织的MTA1蛋白表达,分析其与胃癌发生发展、浸润转移的关系.结果显示,MTA1蛋白在正常胃黏膜、癌旁非典型增生和胃癌组织中的表达率分别为5.00%、22.58%和67.16%,组间比较均有统计学差异(P均<0.05);MTA1蛋白表达与胃癌浸润程度、分化程度及淋巴结转移密切相关(P均<0.05).提示MTA1参与胃癌的发生发展.     

胃癌组织中MTA1,PTEN,E-cadherin的表达及其相互关系

目的:观察MTA1,PTEN,E-cadherin蛋白在胃癌和正常胃黏膜组织中的表达,探讨其与胃癌浸润、转移和生物学行为的关系.方法:应用免疫组织化学方法检测54例胃癌手术切除标本和15例正常胃黏膜组织中MTA1,PTEN,E-cadherin的表达.各指标之间相关因素的差异性比较采用χ2检验,相关性研究采用Spearman相关分析:结果:与正常胃组织相比,MTA1蛋白在胃癌组织中高表达(46.3% vs 6.7%,P＜0.01),PTEN和E-cadherin蛋白在胃癌组织中表达下调或缺失(51.9% vs 100%,42.6% vs 100%,均P＜0.01).MTA1和PTEN的阳性表达率与肿瘤浸润深度(P=0.003,P=0.001)、病理分期(P=0.004,P=0.008)、淋巴转移(P=0.000,P=0.001)、远隔转移(P=0.004,P=0.006)、临床分期有关(P=0.001,P=0.000);E-cadherin的正常表达率与肿瘤浸润深度(P=0.027)、病理分化程度(P=0.006)、淋巴转移(P=0.044)、临床分期有关(P=0.000).Spearman相关分析显MTA1与PTEN蛋白、MTA1与E-cadherin蛋白的表达呈负相关(r=-0.518,r=-0.424,均p＜0.05).PTEN蛋白与E-cadherin蛋白的表达呈正相关(r=0.53,P＜0.05).结论:MTA1蛋白水平高表达和PTEN,E-cadherin蛋白水平低表达可能与胃癌浸润和转移有关,且联合检测可以用于判断胃癌的生物学行为.     

Relationship between cell adhesion molecules expression and the biological behavior of gastric carcinoma

AIM： To evaluate the relationship between the expression of cell adhesion molecules （CAMs） and the biological behavior of gastric carcinoma. METHODS： Expression of syndecan-1, E-cadherin and integrin β3 were evaluated by immunohistochemical study in a total of 118 gastric carcinomas and 20 nontumor gastric mucosas. RESULTS： The expressions of syndecan-1 and E-cadherin were significantly lower in gastric carcinoma compared to non-tumor gastric mucosa, and the low expression rates were positively correlated to the tumor invasion depth, vessel invasion, lymph node metastasis and distant metastasis （P 〈 0.01 in all cases）. However, the expression of integrin β3 was significantly higher in gastric carcinoma compared to non-tumor gastric mucosa, and the high expression rates were positively correlated to the tumor invasion depth, vessel invasion, lymph node metastasis and distant metastasis （P 〈 0.01 in all cases）. In addition, the three protein expressions were correlated to the tumor growth pattern （P 〈 0.01, P 〈 0.01, and P 〈 0.05 respectively）, but not correlated to tumor differentiation （P 〉 0.05, P 〉 0.05 and P 〉 0.05 respectively）. Positive correlation was observed between the expressions of syndecan-1 and E-cadherin, but they which were negatively correlated to the expression of integrin β3 （P 〈 0.01 in all cases）. Univariate analysis demonstrated that the mean survival time and 5-year survival rate were lower in the cases with low expressions of syndecan-1 and E-cadherin and high expression of integrin β3 （P 〈 0.01, in all cases）. COX multivariate analysis showed that the expression level of syndecan-1 could be an independent prognostic index of gastric carcinoma （P 〈 0.01）, whereas E-cadherin and integrin β3 could not be independent indexes （P 〉 0.05, P 〉 0.05 respectively）.CONCLUSION： The low expression of syndecan-1 and E-cadherin and the high expression of integrin β3 are significantly correlated with the invasion and metastasis o     

Expression of somatostatin mRNA in various differentiated types of gastric carcinoma

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胃癌组织中EphA2基因的表达及其与细胞凋亡、增殖的关系

目的 探讨EphA2基因在胃癌组织中表达的生物学意义及与细胞凋亡、增殖的关系.方法 利用免疫组织化学法(immunohisochemistory,IHC)检测82例胃癌手术切除标本的癌组织、癌旁组织及正常胃黏膜中EphA2的表达,采用逆转录聚合酶链反应(RT-PCR)及Western印迹技术对其中随机选取的30例标本进行EphA2 mRNA及其蛋白的定量检测,分析其表达与临床病理参数的关系.采用流式细胞术(FCM)检测82例癌组织中细胞凋亡率及增殖指数(PI),分析EphA2表达与细胞凋亡、增殖的关系.结果 IHC结果显示EphA2在癌组织中的表达显著高于癌旁组织及正常胃黏膜(P<0.01),且随胃癌分化程度降低、浸润深度增加及淋巴结转移而升高(P<0.05),但与肿瘤大小、患者年龄无关(P>0.05);RT-PCR结果显示EphA2 mRNA在各组中的表达水平无显著性差异(P>0.05);Western印迹与IHC结果一致,显示EphA2蛋白在癌组织中异常高表达(P<0.01).FCM结果显示EphA2高表达组细胞凋亡率显著低于低表达组(P=0.018),而其PI显著高于低表达组(P=0.002).结论 EphA2在胃癌组织中表达明显上调,可抑制细胞凋亡,促进细胞增殖,在胃癌的发生发展中发挥重要作用,其机制与EphA2 mRNA的转录异常无关,而可能是其翻译水平上调或蛋白质稳定性增高所致.     

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

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Expression of insulin-like growth factor binding protein-2 in gastric carcinoma and its relationship with cell proliferation

INTRODUCTION The insulin-like growth factor (IGF) system plays a crucial role in normal cell proliferation and malignant transformation[1,2]. It comprises IGF-Ⅰand IGF-Ⅱ, the typeⅠand Ⅱ receptors[3], and a family of IGF binding proteins (IGFBPs) that …     

Alteration of cyclin D1 in gastric carcinoma and its clinicopathologic significance

AIM: To detect the genetic alteration and abnormal expression of cyclin D1 in gastric carcinoma and investigate its clinicopathologic significance in advanced gastric carcinoma. METHODS: Proteins of cyclin D1 were detected by immunohistochemistry in 42 cases of advanced gastric carcinoma with their follow-up data available, 27 cases of early stage carcinoma, 21 cases of gastric adenoma, 22 cases of hyperplastic polyp and 20 cases of normal mucosa adjacent to adenocarcinomas. Genetic alteration of cyclin D1 was detected by Southern blot and expression of cyclin D1 mRNA was detected by PT-PCR in 42 cases of advanced gastric carcinoma. RESULTS: Cyclin D1 protein was not expressed in normal mucosa, hyperplastic polyp and gastric adenoma, while it was only positively expressed in gastric carcinoma. The expression rate of cyclin D1 protein in early stage gastric carcinoma, advanced gastric carcinoma and lymph node metastasis was 48.1%, 47.4% and 50.0%, respectively. The amplification of cyclin D1 gene was detected in 16.6% of advanced gastric carcinomas. The overexpression of cyclin D1 mRNA was detected in 40.5% of the samples. There was no significant correlation between cyclin D1 protein expression and age, lymph-node metastasis and histological grading in patients with advanced gastric carcinoma (chi2 = 0.038, 0.059, 0.241, P>0.05). Significant correlation was observed between the expression of cyclin D1 protein and the 5-year survival rate (chi2 = 3.92, P<0.05). CONCLUSION: Detection of cyclin D1 protein by immunohistochemistry may be useful in the diagnosis of early gastric carcinomas. Patients with positive expression of cyclin D1 protein tend to have a worse prognosis.     

DNA ploidy analysis and expression of MMP-9, TIMP-2, and E-cadherin in gastric carcinoma

AIM: To investigate DNA ploidy and expression of MMP-9, TIMP-2, and E-cadherin in gastric carcinoma and to explore the mechanism of invasion and metastasis of gastric carcinoma. METHODS: Immunohistochemical methods were used to detect the expressions of MMP-9, TIMP-2, and E-cadherin in 156 cases, including 99 cases of gastric carcinoma, 16 cases of adjacent noncancerous mucosa, 16 cases of distant metastases and 25 cases of metastatic lymph node (LN) from gastric carcinoma. Flow cytometry DNA ploidy and S-phase fraction (SPF) analysis were performed on 57 cases, including 47 cases of gastric cancer, 6 cases of adjacent noncancerous mucosa, and 4 cases of distant metastatic cancer. RESULTS: The expression of MMP-9 was significantly correlated with Lauren's classification, Borrmann's classification, LN metastasis, tumor metastasis, and TNM stage, as well as depth of invasion (all P<0.05). The positive rate was lower in noncarcinoma than in carcinoma (31.3% vs66.7%, P<0.01). The expression of TIMP-2 was significantly correlated with Borrmann's classification, LN metastasis, and the depth of invasion (all P<0.05), The expression of E-cadherin was significantly correlated with differentiation, Lauren's classification, Borrmann's classification, and LN metastasis, as well as the depth of invasion (P<0,01 or P<0.05). E-cadherin was less expressed in carcinoma than in noncarcinoma (42.4% vs87.5%, P<0.01). There was a positive correlation between MMP-9 and TIMP-2 and a negative correlation between MMP-9 and E-cadherin, but no correlation between TIMP-2 and E-cadherin. Also there was a positive correlation between DNA aneuploid rate and differentiation and LN metastasis. SPF that was higher than 15% was positively correlated with tumor size, differentiation and LN metastasis. And there was a significant difference between carcinoma and noncarcinoma in DNA aneuploid rate and SPF. CONCLUSION: With tumor progression and development of heterogeneity, the abnormal expressions of MMP-9, TIMP-2, and E-cadherin or DNA aneuploid rate or high SPF gradually increases, suggesting that they play a crucial role in gastric carcinoma progression.