乙酰肝素酶基因表达与胃癌临床病理特点的关系

目的探讨乙酰肝素酶基因(HPAmRNA)在胃癌中的表达及其与临床病理因素之间的相互关系。方法选用43例胃癌组织和10例癌旁正常胃组织,用逆转录聚合酶链反应(RTPCR)检测标本中HPAmRNA的表达,并结合患者临床病理指标进行分析。结果43例胃癌中,29例HPAmRNA表达阳性,其阳性率显著高于癌旁正常胃组织(P=0.013)。HPAmRNA的表达与TNM分期、有无浆膜浸润、淋巴结转移、远处转移以及与肿瘤大小有相关性(P<0.05);与患者年龄、性别、肿瘤所在部位、肿瘤的Borrmann分型、组织学类型、分化程度、腹膜转移和肝转移无相关性(P>0.05)。结论HPAmRNA阳性表达的胃癌有较高的侵袭转移性,HPA可能是胃癌侵袭转移中的一个重要酶,可能与胃癌的淋巴结转移有关。     

乙酰肝素酶mRNA表达和血管生成与胃癌发展的关系

目的　探讨乙酰肝素酶mRNA表达状况和血管生成与胃癌发展的关系。方法　应用原位杂交技术 ,检测 5 2例胃癌组织中乙酰肝素酶mRNA的表达情况 ,并用免疫组化法对全部标本用CD34抗体进行肿瘤血管内皮染色 ,计数肿瘤微血管密度 (MVD) ,分析乙酰肝素酶mRNA与MVD及其与胃癌组织分化程度、浸润深度、淋巴结转移和器官转移的关系。结果　胃癌组织乙酰肝素酶mRNA阳性表达 2 5例 (4 8.1% ) ,MVD平均值为 73.2± 2 2 .8;阴性表达 2 7例 (5 1.9% ) ,MVD平均值为 4 4 .8±11.9,两者之间差异有显著性 (P <0 .0 0 1)。乙酰肝素酶mRNA表达和MVD与胃癌组织浸润深度、淋巴结转移有关 (P <0 .0 0 5 )。结论　乙酰肝素酶与胃癌的血管生成密切相关 ,对胃癌的生长和浸润转移有促进作用 ,乙酰肝素酶可作为反映胃癌生物学行为的客观指标。     

结直肠癌组织中肝素酶mRNA基因表达及其临床意义

目的:探讨结直肠癌组织中肝素酶mRNA表达及其与结直肠癌临床病理参数的关系。方法:采用逆转录聚合酶链反应(RT-PCR)及原位杂交技术检测62例结直肠癌组织及41例癌旁组织中肝素酶mRNA的表达。结果:肝素酶mR-NA在结直肠癌组织中的阳性表达明显高于癌旁组织(P<0·05),且其表达与结直肠癌Dukes分期、淋巴结转移有关(P<0·05)。结论:肝素酶促进了结直肠癌的生长、浸润及转移,与预后不良的病理特征有关。     

胃癌和癌旁组织CD40表达及其生物学意义

[目的]研究CD40及其mRNA在胃癌和癌旁正常组织中的表达.[方法]应用免疫组化技术检测56例胃癌组织和32例癌旁正常组织中CD40分子表达,采用RT-PCR法分别检测¨例胃癌和癌旁正常组织中CD40mRNA的表达.[结果]免疫组化检测显示CD40分子在胃癌组织中的阳性表达率为33.9%(19/56),与癌旁正常组织(6.3%)相比,差异有显著性(P＜0.01);RT-PCR检测发现CD40mRNA在胃癌组织中的阳性表达率为72.7%,在癌旁正常组织中无表达.CD40和CD40mRNA阳性表达均与淋巴结转移及远处转移有关,与肿瘤大小、分化程度、浸润深度无关.[结论]检测胃癌组织中CD40及其mRNA有助于胃癌诊断、预后评价.     

乙酰肝素酶的表达与肝癌侵袭转移及预后的关系

目的探讨乙酰肝素酶(Heparanase Hpa)在肝癌中的表达及其与肝癌临床病理特征的关系。方法分别采用RT-PCR和免疫组织化学法检测Hpa mRNA及Hpa蛋白在肝细胞肝癌、癌旁肝组织及肝癌细胞株中的表达。结果肝癌Hpa mRNA的表达显著高于癌旁及正常肝组织(P<0.05),肝癌组织中Hpa mRNA的表达与肿瘤包膜受侵、门脉受侵、肝内转移、TNM分期、复发有关(P<0.05)。肝癌Hpa蛋白的表达与包膜和门脉是否受侵、Edmondson分级、有无肝内转移、TNM分期及复发有关(P<0.05)。结论Hpa mRNA及蛋白在肝癌中高表达,并与肝癌的侵袭转移、复发、预后有关。     

Heparanase expression is an independent prognostic factor in patients with invasive cervical cancer.

BACKGROUND: Endoglycosidic heparanase degrades heparan sulfate glycosaminoglycans, and may be important in cancer invasion and metastasis, although its expression in human cervical cancer has not been characterized. MATERIALS AND METHODS: Heparanase association with clinicopathological features related to prognostic significance was examined in patients presenting with invasive cervical cancer. Gene expression of heparanase was assessed by RT-PCR in 10 normal cervix and 92 invasive cervical cancer samples. RESULTS: Heparanase mRNA expression was not detected in any of the normal cervix specimens, but was significantly higher in advanced-stage tumors (P = 0.026). In cases treated with radical hysterectomy and pelvic lymphadenectomy, heparanase mRNA expression was significantly higher in tumors exhibiting lymph-vascular space invasion (P = 0.01). A significant relationship was found between microvessel counts and heparanase mRNA expression (P = 0.035). The disease-free and overall survival rates of patients exhibiting heparanase mRNA expression were significantly lower than those of patients lacking heparanase mRNA expression (P = 0.019 and 0.017, respectively). Furthermore, multivariate analysis showed that heparanase mRNA expression was an independent prognostic factor for both disease-free and overall survival. CONCLUSIONS: These findings provide evidence that heparanase expression can serve as an indicator of aggressive potential and poor prognosis in cervical cancer. Consequently, heparanase inhibitor will be a novel candidate for therapeutic intervention in this disease.     

肝素酶在人非小细胞肺癌组织中的表达研究

目的 探讨肝素酶(heparanase，Hpa)在人非小细胞肺癌组织中的表达及其与患者临床病理特征之间的关系，明确其对肺癌患者预后的意义。方法 采用免疫组织化学染色(S-P法)和Western blot检测122例人非小细胞肺癌石蜡包埋组织和38例新鲜肺癌组织及相应癌旁正常肺组织中肝素酶的表达情况，并用x^2检验、Cox比例风险模型和生存曲线等方法分析肝素酶在肺癌组织中的表达意义。结果 肝素酶主要表达在癌细胞膜和/或细胞浆中。免疫组织化学结果表明：在122例非小细胞肺癌组织中有96例(78．7%)呈肝素酶阳性表达，而癌旁正常支气管和肺泡上皮中无阳性表达。Westcrn blot结果亦证实肝素酶在肺癌叶的表达较癌旁正常肺组织明显增高(P=0．043)。x^2检验显示肝素酶表达与肺癌的临床分期(P=0．025)、淋巴结转移(P=0．002)和血管浸润(P=0．0003)有密切关系。生存曲线分析表明肝素酶阳性表达组患者的5年生存率明显低于阴性组(P=0．0006)。但多因素分析结果显示仅肺癌的分期、淋巴结转移和血管浸润可作为影响患者预后的风险因素。结论 肝素酶在人肺癌组织中的表达较正常肺组织明显上调，并与肺癌的临床分期、侵袭、转移和患者的预后相关，但不能作为患者预后评估的独立指标。     

Expression of heparanase and its clinical significance in human non-small cell lung cancer

Objective： To explore the expression and significance of heparanase in non-small cell lung cancer （NSCLC） regarding prognosis and clinicopathological parameters. Methods： The expression of heparanase was assessed using immunohistochemistry staining and Western blot in 122 paraffin-embedded specimens and 38 freshly taken tissues. The relationship between heparanase expression and the clinicopathological factors was analyzed by Chi-square test, multivariate analysis and Kaplan-Meier method. Results： In the immunoreactive cells, staining was mainly located in cytoplasma and membrane. Human heparanase was highly expressed in lung cancer tissue （78.7%, 96/122） while negative in epithelia of normal lung tissues. The level of heparanase was remarkably higher in NSCLC than that in normal tissue （P=0.043）. Expression of heparanase significantly correlated with TNM stage （P=0.025）, lymphatic metastasis （P=0.002） and vascular invasion （P=0.0003）. The patients with positive heparanase expression had a significantly shorter survival than those with negative heparanase expression （P=0.0006）. In multivariate analysis, only p-TNM stage, lymphatic metastasis and vascular invasion could be considered as prognostic factors. Conclusion： Elevated level of heparanase in human non-small cell lung cancer tissues correlates with the TNM stage, invasion, metastasis and prognosis. However, heparanase expression is not an independent prognostic factor.     

血管内皮生长因子C在胃癌中的表达及其与淋巴结转移的关系

目的 研究血管内皮生长因子C(VEGF-C)在胃癌中的表达并探讨其与淋巴结转移的关系。 方法应用逆转录-聚合酶链反应(RT-PCR)检测VEGF-Cm RNA在5株胃癌细胞株中的表达情况,同时采用免疫组化法,检测63 例接受根治性切除手术病例的胃癌组织标本VEGF-C蛋白表达。 结果 VEGF-C mRNA表达于胃癌细胞株MKN-45、SGC-7901及AGS。VEGF-C蛋白则在52．4％(33／63)的病例中呈阳性表达。在 伴淋巴结转移的胃癌中,VEGF-C表达较无淋巴结转移者更显著(P<0．01)。同时,VEGF-C表达与淋巴管浸润和TNM分期密切相 关(P<0．01),但与年龄、性别、肿瘤大小、位置、Lauren分型、浸润深度和血管浸润均无明显相关。 结论 VEGF-C的表达与胃癌淋巴结转移密切相关,同时,淋巴管生成可能成为治疗胃癌的一个新靶点。     

血管内皮生长因子C在胃癌中的表达及其与淋巴结转移的关系

目的研究血管内皮生长因子 C(VEGF-C)在胃癌中的表达并探讨其与淋巴结转移的关系。方法应用逆转录-聚合酶链反应(RT-PCR)检测 VEGF-Cm RNA 在5株胃癌细胞株中的表达情况,同时采用免疫组化法,检测63例接受根治性切除手术病例的胃癌组织标本 VEGF-C 蛋白表达。结果 VEGF-C mRNA 表达于胃癌细胞株 MKN45、SGC-7901及 AGS。VEGF-C 蛋白则在52.4%(33/63)的病例中呈阳性表达。在伴淋巴结转移的胃癌中,VEGF-C 表达较无淋巴结转移者更显著(P<0.01)。同时,VEGF-C 表达与淋巴管浸润和 TNM 分期密切相关(P<0.01),但与年龄、性别、肿瘤大小、位置、Lauren 分型、浸润深度和血管浸润均无明显相关。结论 VEGF-C 的表达与胃癌淋巴结转移密切相关,同时,淋巴管生成可能成为治疗胃癌的一个新靶点。     

乙酰肝素酶与大肠癌浸润、转移和血管生成的相关性

 目的 探讨乙酰肝素酶与大肠癌浸润、转移和血管生成之间的关系。方法 应用原位杂交方法检测乙酰肝素酶mRNA在95例大肠癌组织中的定位及表达。并用免疫组化方法对全部标本进行CDl05染色，记数肿瘤微血管密度（microvessel density，MVD），分析乙酰肝素酶mRNA表达与大肠癌浸润、转移和MVD之间的关系。结果 95例大肠癌组织中，乙酰肝素酶mRNA阳性表达49例（51．57％），MVD平均值为（72．1±20．6）；阴性表达46例（48．42％），MVD平均值为（41．3±12．4），差异有统计学意义（P〈0．01）。乙酰肝素酶tuRNA表达与大肠癌组织浸润深度、淋巴结转移及MVD有关（P〈0．05）。结论 乙酰肝素酶可促进大肠癌的浸润、转移和血管生成，可作为反映大肠癌生物学行为的客观指标。     

激活增强子结合蛋白4在胃癌中的表达及其临床意义

目的:探讨激活增强子结合蛋白4（activating enhancer binding protein 4,AP4）在胃癌组织中的表达及其与临床病理特征的关系。方法:采用RT-PCR和Western blot检测胃癌细胞株BGC823和正常胃上皮细胞中AP4 mRNA和蛋白的表达;应用RT-PCR及免疫组化法检测90例胃癌组织中AP4 mRNA和蛋白的表达;进一步采用Log-rank检验和Cox回归模型对结直肠癌患者的预后因素进行分析,并用Kaplan-Meier计算不同AP4表达情况患者的生存率曲线。结果:与正常胃上皮细胞相比,胃癌细胞株BGC823中AP4 mRNA和蛋白的表达水平均显著升高（均P＜0.05）;在胃癌组织中,AP4 mRNA的表达水平也明显高于配对的癌旁组织（3.848±0.426 vs 1.411±0.405,P＜0.05）;在蛋白水平,胃癌组织也显著高于配对的癌旁组织,且AP4蛋白表达与胃癌的脉管浸润（P＜0.05）、浸润深度（P＜0.05）及TNM分期（P＜0.05）相关,而与患者的性别、年龄、分化程度、肿瘤位置、淋巴结转移和远处转移无关（均P＞0.05）;Kaplan-Meier 单因素回归分析显示,AP4蛋白是影响胃癌患者预后的重要因素（P＜0.05）,进一步Cox多因素回归分析显示AP4蛋白是胃癌患者的独立预后因素（P＜0.05）。结论:AP4高表达与胃癌的发生、发展、转移及预后关系密切,可能成为协助胃癌诊断和治疗的新的生物标志物。     

膜联蛋白Ⅱ在胃癌组织中的表达及其在胃癌转移中的作用

目的：探讨膜联蛋白Ⅱ（AnnexinⅡ）在胃癌组织中的表达及其在胃癌转移中的作用。方法采用免疫组织化学法检测AnnexinⅡ在51例胃癌组织和24例癌旁组织中的表达,并统计AnnexinⅡ阳性表达与胃癌患者临床特征的关系。用AnnexinⅡ特异性siRNA在胃癌HGC-27细胞抑制AnnexinⅡ的表达,应用黏附实验、侵袭实验检测抑制AnnexinⅡ表达后对胃癌细胞的黏附、侵袭能力的影响。结果 AnnexinⅡ蛋白在胃癌组织中阳性率为82.4%,在癌旁组织中阳性率为37.5%,两组比较差异有统计学意义（P﹤0.01）;并且AnnexinⅡ阳性表达与患者的性别与年龄无关（P﹥0.05）,而与肿瘤大小、组织分化程度、临床分期、淋巴结转移临床特征有关,差异具有统计学意义（P﹤0.05）。在胃癌HGC-27细胞转染AnnexinⅡsiRNA后,细胞中AnnexinⅡ的蛋白和mRNA水平均下降,差异有统计学意义（P﹤0.05）。并且抑制AnnexinⅡ表达后,胃癌HGC-27细胞的黏附、侵袭能力下降,差异有统计学意义（P﹤0.05）。结论 AnnexinⅡ在胃癌组织中高表达,AnnexinⅡ蛋白表达与肿瘤大小、组织分化程度、临床分期、淋巴结转移临床特征有关,并且AnnexinⅡ高表达可促进胃癌转移。因此,AnnexinⅡ可以作为抑制胃癌转移的潜在靶点,开发靶向AnnexinⅡ的药物可能成为治疗胃癌转移的新方法。     

骨桥蛋白mRNA在胃癌中的表达及其临床意义

目的 研究胃癌中骨桥蛋白(OPN)mRNA的表达及其与临床病理特征之间的关系,阐明骨桥蛋白在胃癌侵袭和转移过程中的作用。方法 应用半定量RT-PCR方法,检测OPN mRNA在胃癌组织中的表达和相对含量,分析OPN mRNA的相对含量与胃癌临床病理特征的关系。结果 66例胃癌组织中,50例标本可扩增出330bp的条带,OPN mRNA的阳性表达率为75．8％(50／66)。20例正常胃黏膜组织OPN mRNA的表达全部为阴性。OPN mRNA的表达与肿瘤侵袭深度、肿瘤直径、淋巴结转移程度及有无远处转移有关,与肿瘤的分化程度无关。66例患者随访10～27个月(平均16个月)。OPN mRNA表达阳性组50例中复发15例,表达阴性组16例中仅复发1例(P=0．05);OPN mRNA表达阳性组中死亡10例,表达阴性组无一例死亡(P=0．05)。结论 胃癌中,骨桥蛋白mRNA的表达增高。OPN mRNA的高表达反映了胃癌病情的进展,并且与患者的预后有关。骨桥蛋白在胃癌的远处转移过程中可能起着重要的作用。     

Periostin is down-regulated in high grade human bladder cancers and suppresses in vitro cell invasiveness and in vivo metastasis of cancer cells

We have previously reported that expression of periostin mRNA is markedly reduced in a variety of human cancer cell lines, suggesting that downregulation of periostin mRNA expression is correlated with the development of human cancers. In our study, to clarify the role of the periostin in human bladder carcinogenesis, we examined the expression of periostin mRNA in normal bladder tissues, bladder cancer tissues and bladder cancer cell lines by Northern blot analysis and RT-PCR analysis. Although the expression of periostin mRNA was detected in 100% (5/5) of normal bladder tissues, it was not detected in 3 human bladder cancer cell lines examined. It was also detected in 81.8% (9/11) of grade 1, 40.0% (4/10) of grade 2 and 33.3% (4/12) of grade 3 bladder cancer tissues, indicating that downregulation of periostin mRNA is significantly related to higher grade bladder cancer (p<0.05). To assess the tumor suppressor function of periostin, we investigated the ability of periostin gene to suppress malignant phenotypes of a bladder cancer cell line, SBT31A. Ectopic expression of periostin gene by a retrovirus vector suppressed in vitro cell invasiveness of the bladder cancer cells without affecting cell proliferation and tumor growth in nude mice. Periostin also suppressed in vivo lung metastasis of the mouse melanoma cell line, B16-F10. Mutational analysis revealed that the C-terminal region of periostin was sufficient to suppress cell invasiveness and metastasis of the cancer cells. Periostin may play a role as a suppressor of invasion and metastasis in the progression of human bladder cancers.     

Heparanase mRNA and Protein Expression Correlates with Clinicopathologic Features of Gastric Cancer Patients: a Metaanalysis

Background: Heparanase is believed to be involved in gastric carcinogenesis. However, the clinicopathologic features of gastric cancer with high heparanase expression remain unclear. Aim : The purpose of this study was to comprehensively and quantitatively summarize available evidence for the use of heparanase mRNA and protein expression to evaluate the clinicopathological associations in gastric cancer in Asian patients by meta-analysis. Materials and Methods: Relevant articles listed in MEDLINE, CNKI and the Cochrane Library databases up to MARCH 2015 were searched by use of several keywords in electronic databases. A meta-analysis was performed to clarify the impact of heparanase mRNA and protein on clinicopathological parameters in gastric cancer. Combined ORs with 95%CIs were calculated by Revman 5.0, and publication bias testing was performed by stata12.0. Results: A total of 27 studies which included 3,891 gastric cancer patients were combined in the final analysis. When stratifying the studies by the pathological variables of heparanase mRNA expression, the depth of invasion (633 patients) (OR=4.96; 95% CI=2.38-1.37; P<0.0001), lymph node metastasis (639 patients) (OR=6.22; 95%CI=2.70–14.34, P<0.0001), and lymph node metastasis (383 patients) (OR=6.85; 95% CI=2.04-23.04; P=0.002) were all significant. When stratifying the studies by the pathological variables of heparanase protein expression, this was the case for depth of invasion (1250 patients) (OR=2.76; 95% CI=1.52–5.03; P=0.0009), lymph node metastasis (1178 patients) (OR=4.79 ; 95% CI=3.37-6.80, P<0.00001), tumor size (727 patients) (OR=2.06 ; 95% CI=1.31-3.23; P=0.002) (OR=2.61; 95% CI=2.09-3.27; P=0.000), and TNM stage (1233 patients) (OR=6.85; 95% CI=2.04-23.04; P=0.002). Egger’s tests suggested publication bias for depth of invasion, lymph node metastasis, lymph node metastasis and tumor size of heparanase mRNA and protein expression. Conclusions: This metaanalysis suggests that higher heparanase expression in gastric cancer is associated with clinicopathologic features of depth of invasion, lymph node metastasis and TNM stage at mRNA and protein levels, and of tumor size only at the protein level. Egger’s tests suggested publication bias for these clinicopathologic features of heparanase mRNA and protein expression, and which may be caused by shortage of relevant studies. As a result, although abundant reports showed heparanase may be associated with clinicopathologic features in gastric cancer, this meta-analysis indicates that more strict studies were needed to evaluate its clinicopathologic significance.