CD40 signal expression in gastric cancer tissue and its correlation with prognosis of gastric cancer patients

CD40 signaling plays a critical role in the survival rate of gastric cancer patients. Tumour samples were collected from 73 patients with who were diagnosed as gastric cancer in general surgery department in the 1st affiliated hospital of Suzhou University between September 2002 and July 2003. All patients had not received radiotherapy and chemotherapy before operation. These patients include 46 male and 27 female. Here we show that CD40 is constitutively expressed in the human gastric carcinoma tissues, and CD40 protein and mRNA positive expression in gastric cancer tissues closely correlated with lymph node metastasis and tumour TNM stage. CD40 positive expression in gastric cancer patients with lymph node metastasis was markedly higher than that in gastric cancer patients without lymph node metastasis. CD40 positive expression in stage III-IV gastric cancer patients was markedly higher than that in stage I-II gastric cancer patients. Moreover, CD40 expression closely correlated with prognosis of gastric cancer patients. Therefore, CD40 was taken as grouping variable, and lymph node metastasis and clinical staging were taken as stratification variables, respectively, further analysis showed that prognosis in gastric cancer patients with lymph node metastasis and CD40 positive expression was markedly worse than that in gastric cancer patients without lymph node metastasis and CD40 negative expression (P = 0.0076). These results suggest that CD40 signaling plays a critical role in the survival of gastric cancer patients.     

结直肠癌组织ANP32A、Ataxin-3、FHL1的表达及其与肝转移的关系研究

摘要 目的：探讨结直肠癌组织中酸性核磷蛋白32A（ANP32A）、Ataxin-3及4个半LIM结构域蛋白1（FHL1）的表达及其与肝转移的关系。方法：对120例结直肠癌患者癌组织和癌旁组织中ANP32A、Ataxin-3及FHL1蛋白水平进行检测,分析其阳性表达率。其中44例发生肝转移作为肝转移组,76例无肝转移作为无肝转移组,比较两组癌组织中ANP32A、Ataxin-3及FHL1蛋白阳性表达率,分析结直肠癌肝转移的影响因素,分析ANP32A、Ataxin-3、FHL1蛋白之间的相关性。结果：结直肠癌患者癌组织中ANP32A蛋白阳性表达率高于癌旁组织,Ataxin-3、FHL1蛋白阳性表达率低于癌旁组织（P<0.05）。经单因素分析显示肝转移组患者癌组织中ANP32A蛋白阳性表达率显著高于无肝转移组,Ataxin-3、FHL1蛋白阳性表达率显著低于无肝转移组（P<0.05）,肝转移组患者原发癌中低分化、原发癌浸润深度T3~T4、原发癌有淋巴结转移者构成比显著高于无肝转移组（P<0.05）。多因素Logistic回归分析显示,ANP32A蛋白阳性表达、原发癌中低分化、原发癌浸润深度T3~T4、原发癌有淋巴结转移是结直肠癌肝转移的危险因素（P<0.05）,Ataxin-3、FHL1蛋白阳性表达是结直肠癌肝转移的保护因素（P<0.05）。Spearman相关分析显示,结直肠癌患者癌组织中ANP32A阳性表达率与Ataxin-3、FHL1阳性表达率呈负相关（P<0.05）,Ataxin-3蛋白阳性表达率与FHL1蛋白阳性表达率呈正相关（P<0.05）。结论：ANP32A蛋白高表达,Ataxin-3、FHL1蛋白低表达与结直肠癌发生及肝转移有密切关系,且以上指标间具有一定相关性。结直肠癌肝转移受多种因素影响,临床诊治中可根据相关因素为患者制定针对性治疗方案。     

胃癌组织中HER2 基因及p53蛋白表达及其临床意义

目的:研究胃癌组织中HER2基因及P53蛋白表达情况,分析其对临床诊疗的意义与价值。方法:选取2013年7月到2015年7月我院确诊的胃癌患者110例,检测患者胃癌组织中的HER2蛋白表达与基因扩增,及P53蛋白的表达情况,分析HER2基因扩增与P53蛋白表达与病理关系间的关系。结果:HER2基因扩增率为17.3%(19/110),HER2蛋白表达率为42.7%(47/110),P53蛋白表达率为58.2%(64/110),其中HER2蛋白表达3+、2+者HER2基因的扩增比例分别为3/4、6/9与1+表达者的3/16比较具有统计学意义(P0.05);HER2基因扩增和P53蛋白表达与胃癌淋巴结转移以及浸润程度有关(P0.05);相关性分析显示:HER2基因扩增与P53蛋白表达具有正相关关系(P0.05)。结论:胃癌组织中HER2基因扩增和P53蛋白协同表达,促进胃癌浸润和淋巴结转移,对胃癌早期诊断具有重要参考价值。     

PIG11、Caspase-3蛋白在胃癌中的表达及临床意义

目的:探讨PIG11、Caspase-3蛋白在胃癌中的表达及临床意义。方法:采用免疫组织化学SP法检测80例胃癌组织、36例正常胃黏膜组织、30例肠上皮化生组织及31例异型增生组织中PIG11、Caspase-3蛋白的表达水平,并分析其表达与胃癌临床病理特征的关系及两者之间的相关性。结果:胃癌组织中PIG11、Caspase-3蛋白的阳性表达率均显著低于正常胃黏膜、肠上皮化生及异型增生组织(P0.01);PIG11、Caspase-3蛋白表达水平与胃癌的分化程度、临床分期、有无淋巴结转移及远处转移密切相关(P0.05),但与患者的年龄、性别及肿瘤的浸润深度无关(P0.05);PIG11、Caspase-3蛋白在胃癌组织中的表达呈正相关(r=0.859,P0.01)。结论:PIG11、Caspase-3蛋白在胃癌中明显表达下调,且与胃癌的分化程度、临床分期、有无淋巴结转移及远处转移密切相关,可能作为胃癌预后评估的参考指标。PIG11表达下调可能通过抑制Caspase-3的表达促进胃癌的发生和发展。     

VEGF-C 和VEGFR-3 在胃癌组织中的表达及临床意义

目的:探讨胃癌患者血管内皮生长因子C(vascular endothelial growth factor-C,VEGF-C及血管内皮生长因子受体-3(vascular endothelial growth factor receptor-3,VEGFR-3)在胃癌组织中的表达,从而确定胃癌预后的分子标志物。方法:搜集整理临床资料,采用Real-time PCR及ELISA法检测43例胃癌组织VEGF-C和VEGFR-3的表达。结果:43例胃癌组织中均有不同程度的VEGF-C和VEGFR-3的表达,Real-time PCR结果显示胃癌组织淋巴结转移组和非转移组VEGF-C和VEGFR-3的表达分别为0.07±0.01和0.12±0.01,0.03±0.01和0.06±0.02,与正常对照组相比,差异有显著性(p<0.05)。ELISA检测显示,与正常胃组织中VEGF-C和VEGFR-3的蛋白表达相比,胃癌无淋巴结转移组及胃癌并发淋巴结转移组中VEGF-C和VEGFR-3均明显增加。结论:VEGF-C和VEGFR-3的表达与胃癌淋巴结转移密切相关,提示胃癌标本VEGF-C和VEGFR-3的检测可作为胃癌预后的分子标志物。     

Overexpression of ZEB1 associated with metastasis and invasion in patients with gastric carcinoma

The aim of this study was to investigate the expression of ZEB1 in gastric carcinoma, its correlation with the clinicopathology of gastric carcinoma, and the role of ZEB1 in invasion and metastasis in gastric carcinoma. ZEB1 expression was analyzed by immunohistochemistry and Western blot in 45 gastric carcinoma tissue samples that contained the adjacent gastric mucosa. The correlation between ZEB1 expression, the occurrence and development of gastric cancer, and clinical pathology was investigated. ZEB1 expression in the human gastric carcinoma cell line AGS was downregulated by RNA interference, and changes in ZEB1 expression corresponded with changes in the invasive and metastatic ability of AGS cells. Immunohistochemistry revealed that ZEB1 protein expression in gastric carcinoma tissues was significantly higher than in normal gastric mucosa tissues (p < 0.001). A lower degree of differentiation of gastric cancer (p = 0.009), a higher TNM (tumor, node, and metastasis) stage (p = 0.010), and a larger scope of invasion were correlated with higher expression of ZEB1 (p = 0.041, 0.002). However, the expression of ZEB1 in gastric carcinoma tissue was independent of gender, age, and tumor size (p > 0.05). Western blot results also showed that ZEB1 protein expression was significantly higher in gastric carcinoma tissue than in the adjacent normal gastric mucosa tissue (p = 0.008). A lower degree of differentiation of the gastric carcinoma correlated with a higher TNM stage, and a larger scope of invasion correlated with increased ZEB1 expression (p = 0.023). Transfection of ZEB1 siRNA in AGS cells significantly decreased the expression level of ZEB1 protein (p = 0.035). Furthermore, the number of cells that could pass through the Transwell chamber was significantly lower in the transfected group than in the non-transfected control group (p = 0.039), indicating that the suppression of ZEB1 expression could significantly reduce the invasive and metastatic ability of AGS cells (p = 0.005). Concluding, in gastric carcinoma tissue, overexpression of ZEB1 may be related to the occurrence and development as well as invasion and metastasis of gastric carcinoma.     

胃癌组织中Bag-1蛋白表达特点及与临床病理学特征、预后的关系

目的:探讨Bc1-2相联系的抗凋亡基因1(Bag-1)蛋白在胃癌组织中的表达及与患者临床病理学特征、预后的关系。方法:选取病理科收集的79例胃癌组织及30例癌旁组织,标本收集时间2010年2月至2013年12月,采用免疫组化SP染色检测两组标本中的Bag-1蛋白表达水平,并分析Bag-1蛋白表达与胃癌患者临床病理学、预后的关系。结果:胃癌组织中的Bag-1蛋白阳性表达率65.82%显著的高于癌旁组织的13.33%(P0.05);Bag-1蛋白阳性表达的胃癌患者3年生存率30.77%显著的低于阴性表达患者的55.56%(P0.05);Bag-1蛋白阳性和阴性表达的患者1年以及2年生存率相差不大,差异无统计学意义(P0.05);Bag-1蛋白阳性表达的胃癌患者3年生存率30.77%显著的低于阴性表达患者的55.56%(P0.05)。结论:胃癌组织中的Bag-1蛋白高表达,并且与患者的胃癌临床分期和淋巴结转移以及预后有关。     

Twist expression associated with the epithelial-mesenchymal transition in gastric cancer

This study aimed to investigate the expression of Twist in gastric cancer tissues and its correlation between Twist and the epithelial-mesenchymal transition (EMT). By means of RT-PCR and Western blot, the mRNA and protein expressions of Twist, E-cadherin, and Vimentin in 61 gastric cancer tissues and adjacent normal tissues were detected. The positive rates of Twist, E-cadherin, and Vimentin mRNA expression in gastric cancer tissues were 73.9. 40.6, and 60.9 %, respectively; compared to the expression of these genes in adjacent normal tissues (2.9, 75.4, and 27.5 %), the differences were significant (p < 0.05). The E-cadherin protein expression level in gastric cancer tissues was significantly lower than that in the adjacent normal tissues (p < 0.05). After the transfection of Twist siRNA into the MKN45 cells, the protein expression of Twist was significantly reduced (p < 0.05), the protein expression of E-cadherin was significantly increased, and the number of cells that passed through the Transwell chamber was significantly lower than that in the non-transfected control group as well as the transfected control group (p < 0.05). Twist may be associated with the epithelial-mesenchymal transition in gastric cancer and the tumorigenesis, invasion, and metastasis of gastric cancer.     

SRSF1和BIRC5在胃癌组织中的表达及临床意义

目的通过对丝氨酸/精氨酸富有剪接因子1(SRSF1)和凋亡抑制因子(BIRC5)在胃癌组织中表达的检测及两者之间相关性的研究,来探讨两者与胃癌的发生、发展之间的关系;为胃癌的转移及复发预警,以及预后评估提供新靶点。方法应用逆转录-聚合酶链式反应(RT-PCR)和蛋白质印迹(Western blotting)检测60例术中切除的胃癌肿组织以及对应的癌旁组织中SRSF1与BIRC5的表达水平,分析这两种蛋白的表达水平与临床病理学特征的关系。结果 (1)胃癌肿组织中SRSF1 mRNA和BIRC5mRNA表达情况:SRSF1阳性表达率(75.0%,45/60)高于癌旁组织中(8.3%,5/60);BIRC5阳性表达率(81.7%,49/60)高于癌旁组织中(11.7%,7/60)。胃癌肿组织中SRSF1mRNA与BIRC5mRNA的表达与患者的年龄、性别、肿瘤大小等因素无关,与胃癌肿组织的分化程度、淋巴结转移以及TNM分期有关;SRSF1和BIRC5 mRNA在胃癌肿组织中的阳性表达呈正相关(r=0.3496,P=0.0062)。(2)胃癌肿组织中SRSF1蛋白与BIRC5蛋白表达情况:胃癌肿组织中SRSF1蛋白表达量相较于其在癌旁组织中的表达量明显增多(t=44.87,P0.01),BIRC5蛋白表达量较癌旁组织同样异常增高(t=69.84,P0.01)。结论在胃癌肿组织中SRSF1和BIRC5表达均存在异常增高,与胃癌的发生发展存在正相关,这可能与SRSF1选择性剪接BIRC5片段,促进凋亡抑制基因BIRC5的高表达有关,具体机制还需进一步探讨。     

胃癌组织中的MUC1和VEGF表达及其意义

目的:检测胃癌组织中VEGF和MUC1的表达情况,研究二者与胃癌生物学行为之间的关系。方法:应用免疫组织化学SP法检测VEGF和MUC1在胃癌组织和癌旁组织中的表达情况。结果:胃癌组织中VEGF的阳性表达明显高于癌旁组织,两者之间差异存在统计学意义(P0.05),VEGF在胃癌组织中的表达与胃癌浸润深度、有无远处转移、有无淋巴结转移、TNM分期有关,之间差异存在统计学意义(P0.05);胃癌组织中MUC1的阳性表达明显高于癌旁组织,两者之间差异存在统计学意义(P0.05),MUC1在胃癌组织中的表达与分化程度、TNM分期、淋巴结转移、远处转移有关,差异有统计学意义(P0.05);胃癌患者组织VEGF与MUC1的表达水平呈正相关(r=0.210,P0.05)。结论:VEGF和MUC1在胃癌发生、发展和转移过程中起重要作用,可能成为检测胃癌的重要肿瘤标志物。     

TGR5和CDX2在胃黏膜肠化生及胃癌中的表达及意义

目的:探讨G蛋白偶联受体(G protein-coupled receptor,TGR5)和尾型同源盒2(Caudal type homeobox 2,CDX2)在胃黏膜肠化生(Intestinal Metaplasia,IM)及胃癌中的表达和意义。方法:采用免疫组织化学染色法检测TGR5和CDX2在57例慢性胃炎、85例IM、98例胃癌组织中的表达。比较各组间TGR5和CDX2的表达差异,并分析其与胃癌临床病理参数的关系及与胃癌患者预后的关系。利用Spearman秩相关检验分析TGR5和CDX2表达的相关性。结果:IM和胃癌组织中TGR5的高表达率分别为54.1%和58.2%,二者比较无显著差异(P0.05),但均显著高于慢性胃炎组织(P0.01)。TGR5高表达与胃癌患者TNM分期(III+IV期)(P=0.004)、淋巴结转移(P=0.046)及预后较差(P=0.006)相关。胃癌组织中CDX2的高表达率(30.6%)较IM组织(48.2%)显著降低(P0.05),但其均显著高于慢性胃炎组织(P0.01)。CDX2高表达与胃癌患者TNM分期(I+II期)(P=0.008)、无淋巴结转移(P=0.014)、预后较好(P=0.023)相关。TGR5和CDX2表达在慢性胃炎和IM中无相关性(P0.05),在胃癌中呈显著正相关(P=0.003)。结论:TGR5和CDX2在IM和胃癌组织中均显著上调,可能参与了IM和胃癌的发生发展。     

胃癌患者Sox2蛋白和CTHRC-1蛋白的表达与肿瘤发展密切相关

本研究选取病理科收集的自2016年1月至2016年12月的90例术后胃癌组织标本(胃癌组)、45例癌旁组织标本(对照组),采用免疫组化染色法检测两组标本中的Y框蛋白(Sox2)、胶原三股螺旋重叠蛋白-1表达,并分析其与肿瘤TNM分期、淋巴结转移、浸润深度、分化程度的关系,采用Spearman秩相关检验检测两种蛋白的相互关系,试图探讨胃癌患者癌组织中性别决定区Y框蛋白(Sox2)、胶原三股螺旋重叠蛋白-1(CTHRC-1)的表达及其相关性。研究结果表明:胃癌组的Sox2蛋白阳性表达率63.33%显著低于对照组的93.33%(p<0.05),胃癌组的CTHRC-1蛋白阳性表达率78.89%显著高于对照组的24.44%(p<0.05);胃癌组的Sox2蛋白阳性表达与胃癌的分化程度、发生淋巴结转移具有相关性(p<0.05);胃癌组的CTHRC-1蛋白阳性表达与胃癌的淋巴结转移、TNM分期、肿瘤浸润深度具有显著的相关性(p<0.05);胃癌组的Sox2蛋白与CTHRC-1蛋白呈显著的负相关表达(Spearman相关系数r=-0.322, p=0.002<0.05)。本研究的初步结论表明:胃癌组织中Sox2蛋白低表达和CTHRC-1蛋白高表达,并且与肿瘤发展密切相关,且二者表达呈负相关。     

The co-expression of USP22 and BMI-1 may promote cancer progression and predict therapy failure in gastric carcinoma

Recent experimental evidence support the model in which the simultaneous induction of BMI-1 and USP22 is critical during cancer progression. Whether this model may affect gastric cancer (GC) progression is worthy of additional study. In this study, we examined the significance of the USP22 and BMI-1 expression in GC (n = 219), non-cancerous mucosa (n = 37), and lymph node metastasis (n = 37). The protein expression level of USP22 and BMI-1 were concomitantly up-regulated from non-cancerous mucosa to primary carcinoma and from carcinomas to lymph node metastasis (P < 0.001). A statistical correlation was observed between USP22 and BMI-1 expression in GC tissues (n = 219, r = 0.634, P < 0.001) and in lymph node metastasis (n = 37, r = 0.689, P < 0.001). The incidence of positive expression was 57.08% for USP22, 49.32% for BMI-1, and 45.21% for USP22/BMI-1 in 219 GC tissues, respectively. Co-positive of USP22/BMI-1 was significantly correlated with gross features (x(2) = 14.256, P < 0.001), differentiation (x(2) = 5.872, P = 0.015), pT classification (x(2) = 18.486, P < 0.001), pN classification (x(2) = 9.604, P = 0.002), pM classification (x(2) = 32.766, P < 0.001), and AJCC stage (x(2) = 58.278, P < 0.001). Notably, high USP22/BMI-1 expression was significantly associated with shorter disease-specific survival (P < 0.001). By Cox regression analysis, co-positive of USP22/BMI-1 was found to be an independent prognostic factor (P = 0.002). Our results indicated the simultaneous activation of USP22 and BMI-1 may associate with GC progression and therapy failure.     

胃癌组织中溶菌酶的免疫组织化学及其与浸润转移的关系

应用微波－ＳＰ法免疫组化技术,检测了９７例胃癌和３０例手术胃切端正常胃粘膜组织中溶菌酶（ＬＺＭ）表达状况。其阳性率分别为８５．６％和６６．７％,前者显著高于后者（Ｐ＜０．０５）。ＬＺＭ在胃癌中的表达阳性率比较,差分化癌和粘液细胞癌均显著高于分化型腺癌（Ｐ值均＜０．０５）,有淋巴结转移性胃癌显著高于无淋巴结转移者（Ｐ＜０．００５）。在一组原发部位和淋巴结转移性胃癌配对标本中,ＬＺＭ表达无明显差异性,提示胃癌ＬＺＭ活性增高发生在淋巴结转移之前。结果表明,ＬＺＭ表达与胃癌细胞的分化程度及生物学行为密切相关     

幽门螺杆菌感染性胃癌组织中cyclinD1、MMP-9的表达及其临床意义

目的:探讨幽门螺杆菌(HP)感染性胃癌组织中细胞周期蛋白D1(cyclinD1)、基质金属蛋白酶-9(MMP-9)的表达及其临床意义。方法:选取2016年12月到2018年6月期间在兰州大学第一医院接受治疗的胃癌患者80例,收集其手术切除的病理组织。采用C-14呼气试验和改良Giemsa染色检测患者HP感染的情况,采用免疫组化法检测胃癌组织中cyclinD1、MMP-9表达情况。分析HP感染、cyclinD1、MMP-9表达与胃癌患者临床病理特征的关系,并分析胃癌患者HP感染与cyclinD1、MMP-9表达的相关性。结果:80例胃癌患者HP感染阳性56例(70.00%),阴性24例(30.00%)。有淋巴结转移、浸润深度为T3+T4的胃癌患者的HP感染阳性率高于无淋巴结转移、浸润深度为T1+T2的胃癌患者(P0.05)。80例胃癌患者cyclinD1阳性表达45例(56.25%),阴性表达35例(43.75%),MMP-9阳性表达65例(81.25%),阴性表达15例(18.75%),TNM临床分期为III+IV期、分化程度为低分化、有淋巴结转移、浸润深度为T3+T4的胃癌患者的cyclinD1、MMP-9阳性表达率明显高于TNM临床分期为I+II期、分化程度为中高分化、无淋巴结转移、浸润深度为T1+T2的胃癌患者(P0.05)。HP感染阳性患者的cyclinD1阳性表达率和MMP-9阳性表达率均明显高于HP感染阴性患者(P0.05)。Pearson相关分析显示,胃癌患者HP感染与cyclinD1、MMP-9表达均呈正相关(P0.05)。结论:胃癌患者的HP感染情况与淋巴结转移、浸润深度有关,cyclinD1和MMP-9的表达与TNM临床分期、分化程度、淋巴结转移、浸润深度有关,且胃癌患者HP感染与cyclinD1、MMP-9表达均呈正相关。     

抑癌基因PTEN 在甲状腺乳头状癌中的表达及临床意义*

目的:通过免疫组织化学方法检测PTEN基因在正常甲状腺组织、甲状腺良性肿瘤组织、甲状腺乳头状癌癌组织中的表达水平并进行比较,探讨其对甲状腺乳头状癌诊断和治疗的意义。方法:采用SP免疫组化方法,用已知阳性组织做阳性对照,以磷酸盐缓冲液(PBS)代替一抗做阴性对照,分别作HE染色和免疫组织化学染色。结果:PTEN蛋白在三组组织中的表达差异具有显著性(P<0.001);正常甲状腺组织、甲状腺良性肿瘤组织中的阳性率分别为100%和82.5%,均显著高于甲状腺癌组织中的45%(P<0.05),即PTEN在甲状腺癌中表达显著降低;PTEN在甲状腺乳头状癌淋巴结转移组和无淋巴结转移组阳性表达率分别为15%和60%,差异有显著性(x2=10.91,P=0.001);PTEN在甲状腺乳头状癌在包膜侵犯组和无侵犯组的阳性表达率分别为25.93%和60.61%,差异有显著性(x2=7.22,P=0.007);PTEN在甲状腺癌淋巴结转移组和包膜侵犯组的阳性表达强度显著低于无淋巴结转移和包膜侵犯组(P<0.01),有统计学意义。结论:PTEN基因表达的降低在甲状腺癌的发生和转移过程中起重要作用。     

胃癌nm23H1 mRNA、VEGF-C mRNA表达及其与淋巴转移、生存率的相关性研究

研究胃癌组织nm23H1 mRNA、VEGF-C mRNA和VEGFR-3的表达与胃癌中的新生淋巴管的生成、肿瘤淋巴道转移和生存率关系,为临床治疗及预后提供实验依据。用胃癌与癌周组织作对照,应用原位杂交法检测78例胃癌组织nm23H1 mRNA、VEGF-C mRNA表达,并以VEGFR-3抗体为标记,经EnVisionTM免疫组织化学及Leica-Qwin计算机图像分析,用Weidner最高血管密度计数法,计数阳性淋巴管数(MLC),以及调查患者术后的生存率。胃癌nm23H1 mRNA阳性表达 69．23％(54例)、nm23H1 mRNA阳性表达与胃癌淋巴结转移、TNM分期、MLC呈负相关(P<0．01), VEGF-C mRNA阳性表达46．15％(36例),其与胃癌淋巴结转移、TNM分期、MLC呈正相关(P<0．01 或P<0．05)．与癌周组织的nm23H1 mRNA和VEGF-C mRNA表达比较,具有显著性差异(P<0．01 或P<0．05)。nm23H1 mRNA在Ⅰ、Ⅱ期胃癌中呈高表达,在Ⅲ、Ⅳ期患者中呈低或无表达。胃癌组织的MLC(8．37±2．29/mm2)显著高于癌周组织(4．51±2．64/mm2),两者比较具有显著性差异(P<0．05)。 nm23H1 mRNA与VEGFR-3表达之间存在负相关(P<0．05,r=0．8479);VEGF-C mRNA与VEG- FR-3表达之间存在正相关(P<0．05,r=0．8362)。在根治术5年内死亡的61．54％(48例)患者中 MLC(10.82±2．51/mm2)高于5年内生存的患者(6．53±2．09/mm2),两组间有显著性差异(P<0．05);在不同的肿瘤病理学分级中,胃癌未、低分化型与高、中分化型的nm23H1 mRNA阳性表达,有显著性差异(P<0．05),当nm23H1 mRNA高表达时,肿瘤淋巴转移率低,生存率高,故认为nm23H1基因具有抑制胃癌发生和淋巴道转移作用;当VEGF-C mRNA高表达时,肿瘤淋巴转移率高,生存率低。胃癌组织中的VEGFR-3表达水平与肿瘤的淋巴转移密切相关,胃癌组织MLC的显著增高,提示肿瘤组织有新淋巴管的生成。VEGF-C促进了肿瘤诱导的淋巴管新生,在胃癌的淋巴道转移中起重要作用。     

VEGF-C和VEGFR-3在胃癌组织中的表达及临床意义

目的：探讨胃癌患者血管内皮生长因子C（vascular endothelial growth factor-C,VEGF-C及血管内皮生长因子受体-3（vascular endothelial growth factor receptor-3,VEGFR-3）在胃癌组织中的表达,从而确定胃癌预后的分子标志物。方法：搜集整理临床资料,采用Real-time PCR及ELISA法检测43例胃癌组织VEGF-C和VEGFR-3的表达。结果：43例胃癌组织中均有不同程度的VEGF-C和VEGFR-3的表达,Real-time PCR结果显示胃癌组织淋巴结转移组和非转移组VEGF-C和VEGFR-3的表达分别为0.07±0.01和0.12±0.01,0.03±0.01和0.06±0.02,与正常对照组相比,差异有显著性（p〈0.05）。ELISA检测显示,与正常胃组织中VEGF-C和VEGFR-3的蛋白表达相比,胃癌无淋巴结转移组及胃癌并发淋巴结转移组中VEGF-C和VEGFR-3均明显增加。结论：VEGF-C和VEGFR-3的表达与胃癌淋巴结转移密切相关,提示胃癌标本VEGF-C和VEGFR-3的检测可作为胃癌预后的分子标志物。     

中国人胃癌染色体17q21区域基因遗传不稳定性研究

To investigate microsatellite instability (MSI) and loss of heterozygosity (LOH) of locus D17S396, D17S579 and D17S855, and their effect on the expression of nm23H1 and BRCA1 of gastric cancer, which would provide experimental basis for clinical treatment and prognosis analysis of gastric cancer. DNA was extracted from paraffin-embedded materials. Polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) was used to analyze MSI and LOH. Expression of nm23H, and BRCA1 was detected by Envision immuno-histochemistry and Leica-Qwin computer imaging techniques. In the forty cases of gastric cancer, the frequency of MSI, LOH and nm23H1 protein were 20.00%, 17.50% and 55.00% respectively at locus D17S396, while at locus D17S579, the frequency of MSI, LOH and BRCA1 protein were 22.50%, 15.00% and 37.50% respectively; at locus D17S855, the frequency of MSI, LOH and BRCA1 of thirty-seven cases were 18.92%, 18.92%, 37.84% respectively. In tumor node metastasis (TNM) staging, at locus D17S396, D17S579 and D17S855, MSI in stages I + II appeared more frequently than that in stages III + IV, while LOH appeared the contrary tendency. In the group of metastasis of gastric cancer, MSI had a less frequency (5.00%) than that with no metastasis (35.00%, P < 0.05) at locus D17S396, but LOH appeared more frequently (30.00%) than that with no metastasis (5.00%, P < 0.05). At locus D17S579, MSI had an increasing tendency with the degree of tumor differentiation (50.00% in high differentiation cases, 20.00% in middle differentiation cases, and 0% in low differentiation cases, P < 0.05). The frequency of nm23H1 and BRCA1 protein in stages TNM I + II was higher than that in stages TNM III + IV; and that in higher differentiation cases was higher than in poor differentiation cases. The frequency of nm23H1 protein in the group of metastasis (30.00%) was less than that with no metastasis significantly (80.00%, P<0.01). The frequency of nm23H1 protein in the group positive to MSI (87.50%) was higher than that in the group negative to MSI (46.88%, P < 0.05). However, nm23H1 protein in group positive to LOH (14.29%) was lower than that in the group negative to LOH (63.64%, P < 0.05). The frequency of BRCA1 protein in the group positive to MSI (66.67%) was more than that in the group negative to MSI (29.03%, P < 0.05). The results of experiments indicate that MSI and LOH may separately control the development of sporadic colon cancer with different pathways. MSI may be an early period molecule marker for sporadic colon cancer, enhanced expression of nm23H1 protein can effectively inhibit colon cancer metastasis and improve prognosis of sporadic colon cancer patients. By comparison, LOH mostly arises in the late period of sporadic colon cancer and endows a high aggressive and poor prognostic phenotype. nm23H1 protein could effectively restrain gastric cancer metastasis and development; and BRCA1 protein could restain tumor from becoming lower differentiation.