肝素酶mRNA在胃癌组织中的表达及其临床意义

目的　探讨肝素酶 (HPA) m RNA在胃癌组织中的表达及其与胃癌临床、病理特征的关系。方法　以原位杂交技术检测 36例胃癌组织 HPA- m RNA的表达。结果　 HPA- m RNA在胃癌组织中的阳性表达率为72 .2 % ,HPA- m RNA表达与胃癌的浸润程度、TNM分期及分化程度有关 (P<0 .0 5 )。结论　 HPA在胃癌发展过程中起重要作用 ,检测 HPA- m RNA表达有望成为判断进展期胃癌预后的标志     

原发性肝癌组织芯片中乙酰肝素酶的表达及意义

目的:探讨乙酰肝素酶(heparanase,HPA)蛋白在原发性肝细胞癌(HCC)组织芯片中的过度表达及临床意义.方法:125例HCC患者肝组织、48例肝癌患者癌旁组织、62例肝硬化患者肝组织及23例肝血管瘤患者相应正常肝组织构建组织微阵列.应用免疫组织化学检测HPA蛋白的表达水平,并分析其与HCC临床病理特征的关系.结果:HCC组织中的HPA蛋白的阳性率45.83%明显高于癌旁组织27.08%(x~2=2.23,P<0.05),肝硬化6.45%(x~2=5.262,P<0.05)和正常肝组织4.35%(x~2=3.895,P<0.05).癌旁组织中的HPA蛋白阳性率明显高于肝硬化(x~2=2.882,P<0.05)及正常肝组织(x~2=2.361,P<0.05);HCC中临床TNM分期ⅠⅡ期HPA阳性率明显低于ⅢⅣ期(29.41% vs 67.31%,x~2 =4.111,P<0.05);HCC中无转移组HPA阳性率明显低于转移组(14.71% vs 63.33%,x~2= 3.978,P<0.05);HPA表达率在AFP≥400μg/L和AFP<400μg/L组(52.05% vs 36.17%,x~2= 2.071,P<0.05)、有无门脉癌栓组(71.74% vs 29.73%,x~2=4.472,P<0.05)、多个和单个肿瘤结节组(73.91% vs 28.38%,x~2=4.847,P<0.05)以及肿瘤直径≥5 cm和<5 cm组(57.89% vs 25%,x~2=3.471,P<0.01)分别具有显著性意义.HPA表达与年龄、性别、分化程度、有无肝硬化及肿瘤包膜浸润无关.结论:HPA高表达在HCC的发生、发展及转移中起重要作用.检测HPA蛋白指标有助于HCC诊断和判断患者预后.     

乙酰肝素酶在胃癌组织中的表达及临床意义

癌细胞侵袭和转移的一个重要机制是降解基底膜和细胞外基质结构.硫酸乙酰肝素降解性糖苷内切酶的激活与肿瘤细胞转移有关,这在鼠B16-Fl0黑色素瘤细胞在血管内皮细胞细胞外基质上的培养试验中被证实[1].Takaoka等[2]采用逆转录聚合酶链反应(RT-PCR)和免疫组化方法在临床标本和细胞中证明乙酰肝素酶的表达与胃癌的侵袭性和预后不良有关.     

APE表达与胃癌患者预后的关系

目的:研究胃癌患者不同胃黏膜组织无嘌呤无嘧啶核酸内切酶(APE)的表达水平及其变化与预后的相关性.方法:利用已构建好的包含208例胃癌患者胃癌、正常胃黏膜和转移淋巴结的组织芯片,用免疫组化方法检测不同组织APE表达水平,结合患者的生存资料分析APE表达水平和表达水平的变化与预后的关系.结果:患者平均随访时间为48 mo,死亡64例,存活139例,失访5例.在正常胃组织、肿瘤组织和转移淋巴结中,胞核,胞质阳性率以及质核均阳性率分别为96.6%、71.8%、71.4%,97.1%、21.4%、21.4%和98.9%、10.0%、10.0%.正常胃组织、肿瘤组织和转移淋巴结中APE的表达水平以及肿瘤组织和正常组织比较表达水平的变化与患者预后也未显示统计学相关.结论:目前资料未显示APE在不同胃黏膜组织的表达水平和表达水平的变化与胃癌患者预后相关.     

透明质酸合酶1在胃癌组织中的表达及其与胃癌根治术术后患者预后的关系

通过分析透明质酸合酶1(HAS1)在胃癌组织中的表达及其与胃癌患者术后预后的关系, 发现HAS1在胃癌组织中的表达水平高于正常胃黏膜组织。胃癌组织中HAS1表达水平与TNM分期有关, Kaplan-Meier生存分析显示HAS1高表达的患者预后更差。单因素和多因素分析显示, HAS1表达、TNM分期是影响胃癌患者预后的独立危险因素。HAS1关联蛋白质分析发现, HAS1与透明质酸酶1、透明质酸酶2、CD44、透明质酸酶4、精子黏附分子1、肌球蛋白重链10、细胞迁移诱导透明质酸酶1、胶质透明质酸结合蛋白、尿苷二磷酸-葡萄糖脱氢酶、KY蛋白存在相互作用, 提示这些蛋白质可能在胃癌的进展中存在内在联系。在胃癌发生、发展中, HAS1可以作为胃癌患者预后的分子标志物和治疗的潜在靶点。     

应用组织芯片研究凋亡抑制基因Survivin在胃癌中的表达

目的　检测Survivin和CD44v6在胃癌中的表达,以探讨二者在胃癌中表达的相关性及其与预后的关系。方法　利用组织芯片技术构建胃癌组织芯片,应用免疫组织化学S P法检测Survivin和CD44v6蛋白在胃癌中的表达。结果　胃癌中Survivin及CD44v6的总表达率分别为 58 6% (58 /99)和 35 4% (35 /99)。Survivin在早期胃癌中的表达显著高于进展期胃癌 (P<0 05 ),与胃癌的其它临床病理特征无相关性。CD44v6阳性表达与胃癌生长方式(P<0 001)、浸润深度 (P<0 05 )及淋巴结转移 (P<0 001 )密切相关。Sur vivin和CD44v6在胃癌中的表达无相关性(r=-0 065,P>0 05)。Survivin与胃癌患者的生存率无显著相关,而CD44v6表达阳性组 5年生存率(16 13% )显著低于CD44v6表达阴性组 5年生存率(60 67% ) (P<0 001 )。结论　Survivin和CD44v6在胃癌中均有过量表达。Survivin可能参与胃癌发生、发展的早期过程;而CD44v6阳性表达与胃癌的浸润和转移密切相关,同时可以提示胃癌的不良预后。     

乙酰肝素酶在结肠癌组织中的表达与临床病理特征及预后的关系

[目的]探讨乙酰肝素酶（Heparanase，Hpa）在结肠癌组织中的表达及其与结肠癌临床病理特征和预后的关系。[方法]采用S-P免疫组织化学法检测Hpa和CD34蛋白在结肠癌组织和正常结肠黏膜组织中的表达，并结合病理学分型、组织学分级、微血管密度（MVD）和临床分期探讨其意义。[结果]结肠癌Hpa蛋白的表达显著高于正常结肠黏膜（P〈0．05），结肠癌组织中Hpa蛋白的表达与结肠癌组织血管生成、病理分型、Duke＇s分期、预后有关（P〈0．05）。[结论]Hpa蛋白在结肠癌中呈高表达，并与结肠癌血管生成、病理特征和预后有关，检测其表达可以对判断结肠癌的生物学行为提供指标。     

胃泌素及胃泌素释放肽在胃癌组织中的表达及意义

目的 研究胃癌组织中胃泌素（Gastyin，GAS）、胃泌素释放肽（Gastrin releasing peptide，GRP）的表达及其意义。方法采用组织芯片技术制作60例胃癌组织芯片，同时用S—P免疫组织化学方法检测胃癌组织芯片中GAS、GRP的表达。结果 60例胃癌中GAS阳性率为31．7％；GRP阳性率为11．7%。中、低分化胃癌GAS、GRP的表达阳性率高于高分化胃癌（P〈0．05），黏液腺癌、印戒细胞癌GAS、GRP的表达阳性率显著高于其它组织学类型胃癌（P〈0．01），胃癌GAS、GRP阳性表达与淋巴结转移相关（P〈0.05）。结论 本研究结果提示中、低分化胃癌，黏液腺癌、印戒细胞癌可作为胃癌内分泌治疗的主要适应证。     

乙酰肝素酶在胃癌组织中的表达及其与临床病理特征的关系

目的 探讨乙酰肝素酶在胃癌组织中的表达及其与临床病理特征的关系.方法 应用免疫组化方法检测60例胃癌术后组织标本及正常组织中乙酰肝素酶的表达,分析乙酰肝素酶表达与胃癌临床病理特征的关系.结果 胃癌组织中存在乙酰肝素酶蛋白的表达,并定位于肿瘤细胞质中.60例胃癌组织中有40例乙酰肝素酶表达阳性(40/60,66.7％),正常组织有1例表达阳性(1/10,10％),两组间差异显著(P ＜0.05).乙酰肝素酶蛋白在胃癌中的表达与患者性别、年龄、肿瘤直径无关(P＞0.05),与组织学分级、TNM分期、淋巴结转移相关(P＜0.05).结论 乙酰肝素酶在胃癌中高表达,与胃癌进展程度和恶性行为相关,对胃癌的发生、发展起促进作用,可为临床治疗和诊断提供一定依据.     

组织芯片技术在检测胃癌组织中TRAF4表达中的应用

目的探讨组织芯片技术诊断胃癌的价值。方法采用免疫组化法检测胃癌组织芯片（胃正常组织10份、增生组织45份、胃癌组织45份）中肿瘤坏死因子受体相关因子4（TRAF4）的表达。结果 TRAF4胞质阳性率在正常组织、增生组织和胃癌组织中逐渐增高,但差异无统计学意义。胞核阳性率逐渐降低,正常组织显著高于胃癌组织,P〈0.05;胃癌组织中高分化者显著高于低分化者（P〈0.05）,无淋巴转移者显著高于有淋巴转移者,P〈0.05。结论组织芯片可大规模、高效率检测胃癌组织样本,具有快速、方便、经济、准确等特点,可用于胃癌的早期诊断。     

生存素基因在胃癌组织中的表达及其与胃癌预后关系

目的探讨生存素(survivin)基因在胃癌组织中的表达及其与胃癌预后关系。方法病例来源于1995年7月至1996年6月中山医院住院手术患者，采用免疫组化Envision二步法检测手术切除的胃癌病灶组织中生存素基因表达。根据手术病理诊断与临床表现确定肿瘤TNM分期。所有病例随访至少5年或直到死亡。比较不同病理类型、不同TNM分期生存素表达差异。按生存素基因是否表达比较两组患者生存曲线的差异。结果共有96例患者进入研究和随访观察，其中男59例，女37例；年龄29～84岁，平均56岁，68例表达生存素基因产物，阳性率70．8％。病理类型中腺癌78例，非腺癌18例，不同病理类型生存素基因表达相似(腺癌69．7％、非腺癌60．0％，P=0．369)。对腺癌病例分析显示：低分化组生存素基因表达高于中高分化组(82．1％比62．5％，P=0．053)；肿瘤累及固有肌层组和全层组生存素基因表达高于肿瘤局限于黏膜或黏膜下层组(81．3％，75．9％比33．3％，P=0．020)。生存素表达与淋巴结转移与否无关(68．1％比70．8％，P=0．771)。生存素阳性组5年生存率(42．93％)低于生存素阴性组(52．93％)，但差异无统计学意义。结论生存素基因在胃癌中高表达。生存素基因表达与胃腺癌分化程度以及肿瘤累及深度有关，需进行更多研究评价其在预后中的作用。     

肝肠钙粘连蛋白在胃癌组织中的表达及临床意义

目的探讨肝肠钙粘连蛋白在不同分化程度的胃癌、正常胃黏膜组织中的表达及其与胃癌生物学行为的关系。方法采用免疫组化S—P法,检测肝肠钙粘连蛋白在74例胃癌及其正常胃黏膜组织中的表达情况,并结合临床病理资料进行分析。结果74例胃癌组织中肝肠钙粘连蛋白样阳性表达58例,总阳性率为78．4％,而肝肠钙粘连蛋白在正常胃黏膜组织中没有表达。肝肠钙粘连蛋白的阳性表达与胃癌分化程度以及淋巴结是否转移有关（P〈0．05）;而与年龄、性别、TNM分期以及是否有幽门螺杆菌感染、肝转移、腹膜转移间无关（P〉0．05）。结论肝肠钙粘连蛋白在胃癌组织中的表达与胃癌细胞的转移、浸润、生长和粘附有关。肠钙粘连蛋白有助于胃癌分化程度的判断和预测胃癌淋巴结有无转移。     

COX-2 expression in gastric cancer and its relationship with angiogenesis using tissue microarray

AIM： To explore the expression and clinicopathological significance of cyclooxygenase-2 （COX-2） and microvessel density （MVD） in gastric carcinogenesis, and to investigate their roles in the invasion and the relationship between biological behaviors and prognosis of gastric cancer.
METHODS： Using Envision immunohistochemistry, COX-2 and CD34 expressions in gastric cancer tissue array were examined. MVD was counted and the relationship between the biological behaviors and prognosis was analyzed.
RESULTS： The expression of COX-2 in gastric cancer tissue was significantly higher than that in normal mucosa （χ^2 = 12.191, P 〈 0.05）. The over-expression of COX-2 in gastric cancer was obviously related to metastasis and depth of invasion （χ^2 = 6.315, P 〈 0.05）, but not related to the histological type and Borrmann type （χ^2 = 5.391 and χ^2= 2.228, respectively）. Moreover, MVD in gastric cancer tissues was significantly higher than that in the normal mucosa （65.49 ± 20.64 vs 36.21 ± 18.47, t/F = 7.53, P 〈 0. 05）. MVD was related to the histologic type and metastasis （t/F= 3.68 and t/F = 4.214, respectively, P 〈 0. 05）, but not related to the depth of invasion and Borrmann type （t/F = 0.583 and t/F = 0.459, respectively）. MVD in COX-2-positive tissues was markedly higher compared to COX-2-negative tissues, indicating a positive correlation between COX-2 expression and MVD （t = 13.12, P 〈 0. 05）.
CONCLUSION： Tissue microarray （TMA） is a powerful tool for rapid identification of the molecular alterations in gastric cancer. COX-2 expression, via inducingangiogenesis, may play an important role in gastric carcinogenesis. It could be served as a determinant factor for clinical prognosis and curative effect.     

Reduced expression of circulating microRNA-218 in gastric cancer and correlation with tumor invasion and prognosis

AIM:To investigate the expression of microRNA-218(miR-218)in serum from gastric cancer patients and its relationship with clinicopathological characteristics.METHODS:A total of 68 patients with pathologically diagnosed gastric cancer and 56 healthy individuals were recruited to this study.The expression of miR-218was detected in the serum of gastric cancer patients and healthy individuals by quantitative real-time polymerase chain reaction.The clinical data were collectedand analyzed by statistical software.RESULTS:miR-218 was reduced significantly in the serum of gastric cancer patients compared to healthy individuals(1.15±0.08 vs 0.37±0.023;P=0.026).In the gastric cancer group,serum expression of miR-218was lower in patients with metastasis and poorly differentiated cancer compared with non-metastatic and well-differentiated cancer(0.19±0.011 vs 0.45±0.021,P=0.031 and 0.21±0.019 vs 0.49±0.021,P=0.025).Serum miR-218 was found to be significantly associated with gastric cancer metastasis(P=0.003),tumor T stage(P=0.018)and tumor grade(P=0.012).Low serum expression of miR-218 was related to an increase in the stage of gastric cancer.The expression level of miR-218 in the serum was correlated with the3-year survival.Ninety-seven percent of patients with a high level of miR-218 expression survived for 3 years,while only 54%of those with low miR-218 expression survived.CONCLUSION:miR-218 is deregulated in gastric cancer patients and is strongly correlated with tumor stage,grade and metastasis.Serum expression of miR-218 may be a prognostic marker.     

Expression of connective tissue growth factor in tumor tissues is an independent predictor of poor prognosis in patients with gastric cancer

AIM： TO examine the expression of connective tissue growth factor （CTGF）, also known as CCN2, in gastric carcinoma （GC）, and the correlation between the expression of CTGF, clinicopathologic features and clinical outcomes of patients with GC. METHODS： One hundred and twenty-two GC patients were included in the present study. All patients were followed up for at least 5 years. Proteins of CTGF were detected using the Powervision two-step immunostaining method, RESULTS： Of the specimens from 122 GC patients analyzed for CTGF expression, 58 （58/122, 47.5%） had a high CTGF expression in cytoplasm of gastric carcinoma cells and 64 （64/122, 52.5%） had a low CTGF expression. Patients with a high CTGF expression showed a higher incidence of lymph node metastasis than those with a low CTGF expression （P = 0.032）. Patients with a high CTGF expression had significantly lower 5-year survival rate than those with a low CTGF expression （27.6% vs 46.9%, P = 0.0178）, especially those staging Ⅰ ＋ Ⅱ ＋ Ⅲ （35.7% vs 65.2%, P = 0.0027）. CONCLUSION： GC patients with an elevated CTGF expression have more lymph node metastases and a shorter survival time. CTGF seems to be an independent prognostic factor for the successful differentiation of high-risk GC patients staging Ⅰ ＋ Ⅱ ＋ Ⅲ, Over-expression of CTGF in human GC cells results in an increased aggressive ability.     

Expression of gastrin and its receptor in human gastric cancer tissues

Purpose: Gastrin is a growth factor of cancerous and normal cells of the gastrointestinal tract, and its effect is known to be mediated by gastrin/cholecystokinin B (CCKB) receptor. This study was performed to investigate the prognostic significance and the expression profiles of gastrin and gastrin receptor in human gastric carcinoma tissues. Methods: We analyzed the expressions of gastrin and gastrin receptor by immunohistochemical staining using anti-gastrin Ab (Sigma, St. Louis, MO, USA) and anti-gastrin receptor Ab (Aphton Corp., Woodland, CA, USA) in 279 gastric adenocarcinoma patients. Patients’ clinicopathologic features and prognoses were analyzed. Results: The gastrin expression rate in these patients was 47.7% (133/279) and the gastrin receptor expression rate was 56.5% (158/279). Gastrin expression was significantly higher in men than in women (54.3% vs. 34.1%), and higher in differentiated gastric adenocarcinoma than in the undifferentiated type (55.1% vs. 43.0%). The gastrin receptor expression rate was also significantly higher in men than in women (61.2% vs. 47.3%), and was higher in the differentiated type than in the undifferentiated type (72.9% vs. 46.5%), and significantly higher in the intestinal type than in the diffuse type (75.2% vs. 42.9%). Gastrin and gastrin/CCKB receptor expressions were not found to be significant prognostic factors in themselves. When focused on correlation between the co-expression of gastrin and gastrin/CCKB receptor and the survival, the prognosis of patients positive for both gastrin and gastrin receptor was significantly poorer than for those negative for gastrin and gastrin receptor in diffuse-type gastric cancer patients. However, multivariate analysis showed that only TNM stage was an independent prognostic factor of survival in diffuse-type gastric cancer patients. Conclusions: This study shows that the expression rates of gastrin and gastrin receptor are high (about a half) in gastric carcinoma tissues, and that there is an association between gastrin and gastrin receptor expression. We also found that patients with diffuse-type gastric carcinoma tissues expressing both gastrin and gastrin receptor have a poorer prognosis than those negative for both, which suggests that gastrin acts as an autocrine growth factor in a subgroup of gastric carcinomas.     

Bmal1在胃癌组织中的表达及其临床意义

目的 探讨钟基冈Bmal1在胃癌和癌旁组织中的表达及其临床意义.方法 收集15例胃癌和癌旁非癌新鲜手术标本,以实时荧光定量PCR检测Bmall mRNA表达.收集64例胃癌和癌旁组织,以免疫组化方法检测Bmal1表达,用图像分析技术分析Bmal1在不同组织中的表达差异,结合临床资料探讨其与胃癌临床病理的相关性.结果 胃癌组织中Bmal1 mRNA转录量为1.02±0.05,癌旁组织中为0.57-0.03,二者比较差异有统计学意义(P＜0.05).Bmal1蛋白在癌旁组织中主要位于细胞的胞核,平均吸光度值为0.1041 ±0.0543,而在胃癌组织中主要位于胞质,平均吸光度值0.1816±0.0128,Bmall在胃癌组织与癌旁组织差异有统计学意义(P＜0.05).Bmal1表达强度与年龄、胃癌分化程度相关(P＜0.05),Bmal1与性别、肿瘤大小、浸润深度、淋巴结转移无相关性(P＞0.05).结论 Bmal1蛋白在胃癌组织中表达移位和表达上调可能与胃癌发生、发展相关,可能成为影响胃癌预后的重要因素.