柯萨奇病毒-腺病毒受体在结肠癌组织中的表达及意义

目的：柯萨奇病毒-腺病毒受体（coxsackie and adenovirus receptor，CAR）介导腺病毒与靶细胞之间的粘附，是腺病毒转染靶细胞的限速因子。本文分析CAR在瘤旁上皮组织、结肠肿瘤原发灶和淋巴结转移灶中的表达．为设计腺病毒载体基因治疗方案提供依据。方法：采用免疫组织化学方法检测62例结肠癌组织中CAR的表达．分析CAR表达与临床病理特征的关系。结果：与瘤旁上皮组织相比，肿瘤组织普遍存在CAR表达下调．但CAR在原发灶和淋巴结转移灶的表达水平无明显差异。CAR的表达水平与患者年龄及肿瘤大小相关。结论：结肠癌组织中存在CAR表达下调，提示在设计腺病毒载体基因治疗方案时应充分考虑CAR表达变化对疗效的影响.     

长链非编码RNA HOXA-AS3在结肠癌组织中的表达及与临床预后的关系

目的:观察长链非编码RNA HOXA-AS3（lncRNA HOXA-AS3）在结肠癌组织中的表达并探究其与临床预后的关系。方法:选取2012年01月至2014年02月本院外科行手术治疗的94例结肠癌患者癌变及癌旁结肠组织冻存标本,采用实时定量PCR（RT-qPCR）法检测癌组织和癌旁组织中lncRNA HOXA-AS3的表达水平,采用单因素方差分析其与结肠癌患者临床病理参数的关系;采用Kaplan-Meier生存曲线分析lncRNA HOXA-AS3表达水平与结肠癌患者5年生存率的关系;采用COX多因素回归分析影响结肠癌患者不良预后的危险因素。结果:与癌旁组织比较,结肠癌组织中lncRNA HOXA-AS3表达水平明显升高（P＜0.05）;lncRNA HOXA-AS3在结肠癌组织中的表达水平与患者年龄、性别、病理类型无关（P＞0.05）,与TNM分期、肿瘤直径、分化程度、淋巴结转移有关（P＜0.05）。lncRNA HOXA-AS3高表达组结肠癌患者5年生存率（60.98%）明显低于低表达组（94.34%）（χ2=16.41,P＜0.05）。COX回归分析结果显示,lncRNA HOXA-AS3高表达、TNM分期和淋巴结转移是影响结肠癌患者预后的独立危险因素（P均＜0.05）。结论:lncRNA HOXA-AS3在结肠癌组织中高表达,且与患者TNM分期、肿瘤直径、分化程度、淋巴结转移及5年生存率有关,其表达变化可能与结肠癌的发生、发展进程有关,有潜力成为结肠癌预后评估的新型生物指标及潜在治疗靶标。     

膜型-Ⅰ型基质金属蛋白酶mRNA在人喉鳞癌组织中的表达

目的：为研究人喉鳞状细胞癌在其浸润转移中的的生物学行为,探讨能导致肿瘤浸润转移的膜型-Ⅰ型基质金属蛋白酶mRNA在人喉鳞癌组织不同部位的定位及表达情况。方法：采用原位杂交方法对人喉鳞癌组织的原发灶50例、癌旁组织34例、淋巴结22例、正常粘膜20例进行膜型-Ⅰ型基质金属蛋白酶mR-NA的进行检测,图像分析做定量分析。结果：原发灶中MT1-MMP mRNA主要在肿瘤细胞的胞浆中呈强阳性表达,进展期肿瘤癌巢周边的基质细胞中呈弱阳性表达。在癌旁、转移淋巴结的肿瘤细胞胞浆中有阳性表达。原发灶中MT1-MMP mRNA表达与癌旁、正常粘膜组织均有显著差异（P=0.000）;与淋巴结之间存在显著差异（P=0.004）;正常粘膜与淋巴结之间也存在显著差异（P=0.000）;癌旁与淋巴结之间无显著差异（P=0.900）;癌旁与正常组织之间亦无显著差异（P=0.260）。结论：MT1-MMP mRNA在原发灶、癌旁（淋巴结）、正常组织中的表达呈递减趋势。提示其在喉癌浸润转移的生物学行为中有重要作用。     

IL-6在不同Dukes分期结肠癌中的表达及临床意义

目的：探讨不同 Dukes 分期结肠癌组织及癌旁组织中的 IL -6以及结肠癌患者外周血 IL -6的表达情况。方法：收集56例结肠癌、癌旁组织的标本及15例正常结肠组织标本。收集结肠癌患者术前外周血标本和正常对照组外周血标本。采用免疫组织化学 SP 法检测 IL -6蛋白的表达及用酶联免疫吸附（ELISA）法检测血清中 IL -6的水平。结果：结肠癌患者组织 IL -6阳性率显著多于癌旁对照组（P <0.05）及正常对照组（P <0.05）。阳性表达率与淋巴结转移、临床 Dukes 分期有关（P <0.05）,与组织学分级、肿瘤大小无关（P>0.05）;结肠癌外周血 IL -6水平显著高于正常对照组（P <0.05）。结论：IL -6在结肠癌中表达明显增高,且与临床分期有关,可作为诊断结肠癌的预警信号和判断预后的有用指标。     

c-erbB-2蛋白在人结肠癌组织中的表达及其与临床病理关系

目的：探讨人结肠癌组织中c-erbB-2蛋白的表达及其与临床病理的关系。方法：采用免疫组织化学SABC法研究80例人结肠癌组织标本、30例癌旁黏膜组织、30例正常结肠黏膜上皮中c-erbB-2基因的表达。结果：癌组织c-erbB-2阳性表达率明显高于癌旁组织和正常组织（62.5%、26.7%、6.7%,P〈0.05）。c-erbB-2阳性表达率在Dukes C和D期和有淋巴结转移者明显高于Dukes A和B期和无淋巴结转移者（81.8%vs 48.9%,P=0.003）。结论：c-erbB-2在结肠癌组织中的表达有较高的特异性,c-erbB-2基因在分期晚和有淋巴结转移者中表达较高,提示可以作为结肠癌的诊断或预后指标。     

HDAC1和CDK1在结肠癌组织中的表达及其临床意义

目的:研究组蛋白去乙酰化酶1（histone deacetylase 1,HDAC1）和细胞周期蛋白依赖性激酶1（cyclin-dependent kinase 1,CDK1）在结肠癌组织中的表达水平及其与患者临床病理特征及预后的关系。方法:收集2012年2月至2013年6月在本院普外科进行手术切除的51例结肠癌患者的肿瘤组织和癌旁非肿瘤组织，采用qRT-PCR法检测组织中HDAC1和CDK1 mRNA相对表达量，采用免疫组织化学染色法检测HDAC1和CDK1蛋白阳性表达率，分析肿瘤组织中HDAC1和CDK1表达的相关性及其与患者肿瘤直径、淋巴结转移等临床病理特征的关系，采用Kaplan-Meier生存函数分析HDAC1和CDK1不同表达情况与患者5年总生存率的关系。结果:肿瘤组织中HDAC1和CDK1 mRNA表达水平和蛋白阳性表达率均高于癌旁非肿瘤组织（P＜0.05）；肿瘤组织中HDAC1表达水平与CDK1表达水平呈显著正相关（P=0.012）；肿瘤组织中HDAC1表达与患者肿瘤直径和组织分化程度有关（P＜0.05），CDK1与肿瘤直径、TNM分期、分化程度、淋巴结转移有关（P＜0.05）；HDAC1、CDK1阳性表达患者5年总生存率均低于其相应阴性表达患者（P＜0.05），HDAC1和CDK1共阳性表达患者5年总生存率低于HDAC1和（或）CDK1阴性患者（P＜0.05）。结论:HDAC1和CDK1在结肠癌组织中高表达，与患者不良预后有关且两者呈正相关，推测两者在促进结肠癌进展中可能存在协同作用。     

去泛素化酶USP9X在结肠癌组织中的表达及意义

目的:探讨去泛素化酶USP9X在结肠癌组织中的表达特点及对结肠癌细胞增殖的影响。方法:收集解放军中部战区总医院病理科存档的结肠癌组织标本和癌旁正常结肠组织标本76例，免疫组化法检测USP9X在不同性别、年龄患者的结肠癌组织、癌旁正常结肠组织中的表达情况。siRNA抑制人结肠癌HCT116细胞株USP9X的表达，MTT法检测HCT116细胞增殖能力。结果:76例结肠癌患者中，USP9X阳性表达53例，占69.7%。癌旁正常大肠组织中，USP9X阳性表达率19.7%。USP9X的表达与结肠癌淋巴结转移和浸润深度相关。siRNA抑制结肠癌HCT116细胞USP9X表达后，与空白对照组和阴性对照组比较，干扰组细胞增殖能力显著下降。结论:去泛素化酶USP9X在结肠癌组织中的表达高于癌旁正常结肠组织，并与肿瘤侵袭转移相关。特异性抑制USP9X基因的表达可抑制结肠癌细胞的增殖能力。     

食管鳞癌中IDO的表达及其与肿瘤血管形成的关系

目的 检测吲哚胺2,3-双加氧酶（Indoleamine 2,3-dioxygenase, IDO）在人食管鳞癌及其癌旁组织中的表达及规律,通过检测VEGF的表达探索IDO及肿瘤血管形成的相关性,并了解两者在食管鳞癌的进展及转移中的作用。方法 收集56例河北医科大学第四医院行食管切除患者的肿瘤组织及其癌旁组织,使用半定量RT-PCR法和免疫组织化学法检测组织样本中IDO和VEGF的mRNA和蛋白表达情况,并分析在食管鳞癌组织中IDO与肿瘤血管形成的相关性。结果 与癌旁组织相比,食管鳞癌组织中的IDO和VEGF阳性表达率和表达水平均显著升高（P=0.020,P=0.022）,其表达与患者年龄、性别等无关（P＞0.05）,与患者TNM分期、肿瘤侵犯深度、分化程度、淋巴结转移相关（P＜0.05）。食管鳞癌组织中IDO的表达与VEGF的表达呈显著正相关（r=0.533,P=0.001）。结论 在食管鳞癌中IDO可能与肿瘤血管的形成有关。     

结肠癌组织中miR-802和RAB23的表达水平及临床意义

目的:检测微小RNA-802(miR-802)和RAB23在结肠癌组织中的表达水平，探究其临床意义。方法:以本院2014年3月至2015年4月收治的结肠癌患者84例为研究对象，所有患者经诊断后行结肠癌根治术，术中取患者癌组织及癌旁正常组织。实时荧光定量PCR检测miR-802和RAB23 mRNA表达水平，免疫组化分析RAB蛋白表达水平。结果:miR-802在结肠癌组织中的表达水平显著低于癌旁正常组织，RAB23表达水平显著高于癌旁正常组织（P<0.05）；结肠癌组织中RAB23蛋白表达阳性率显著高于癌旁正常组织（P<0.05）；相关性分析表明结肠癌组织中miR-802表达水平与RAB23 mRNA表达水平呈负相关（P<0.05）；miR-802和RAB23表达水平与患者肿瘤大小和淋巴转移情况有关（P<0.05）；结肠癌患者中miR-802低表达者、RAB23阳性表达者生存率分别显著低于miR-802高表达者、RAB23阴性表达者（P<0.05）；COX分析显示miR-802和RAB23表达水平是影响结肠患者不良预后的独立危险因素（P<0.05）。结论:miR-802在结肠癌患者癌组织中表达水平显著降低，RAB23表达水平显著升高，与结肠癌患者预后有关，可为结肠癌患者预后判断提供参考。     

肝癌缺失-1基因表达与结肠癌分期相关性研究

目的 探讨肝癌缺失-1（DLC-1）基因mRNA表达与结肠癌分期及淋巴结转移的相关性.方法 收集2009年9月至2011年9月手术切除结肠癌标本共60例,以外伤、结肠憩室、结肠炎手术治疗留取的正常组织10例为对照.采用反转录PCR定量检测结肠癌组织、癌旁组织、正常组织DLC-1基因mRNA的表达.依据TNM分期进行分期,采用直线相关分析DLC-1基因表达与结肠癌分期及淋巴结转移的相关性.结果 结肠癌组织DLC-1基因mRNA的表达水平（0.085±0.004）明显低于癌旁组织（0.562±0.063）,癌旁组织低于正常组织（1.000±0.003）.DLC-1基因mRNA表达水平与结肠癌分期呈负相关（r=0.51,P＜ 0.01）,DLC-1基因mRNA表达水平与淋巴结转移呈负相关（r=0.46,P＜ 0.05）.结论 DLC-1基因mRNA表达与病理学分期、淋巴结转移率呈负相关,DLC-1基因在结肠癌发生、发展中扮演重要角色,可能是研究结肠癌新的突破口.     

Effect of CXCR4 and CD133 Co-expression on the Prognosis of Patients with Stage Ⅱ~Ⅲ Colon Cancer

Background: To explore the relationship between CXCR4, CD133 co-expression and clinicopathologicalfeatures as well as prognosis of patients with phase Ⅱ~Ⅲ colon cancer. Materials and Methods: Forty-nineparaffin-embedded samples of tumor tissue and epithelial tissue adjacent to cancer were collected frompatients with colon cancer undergoing radical surgery in Baotou Cancer Hospital from January, 2010 to June,2011. CXCR4 and CD133 expression was detected using immunohistochemistry and its relationship withclinicopathological features and the 3-year survival rate was analyzed. Results: In the tumor tissue and colonicepithelial tissue adjacent to cancer, the positive expression rates of CXCR4 were respectively 61.2% (30/49) and8.16% (4/49), while those of CD133 being 36.7% (18/49) and 6.12% (3/49). CXCR4 and CD133 expression intumor tissue was not related to patient age, gender, primary focal sites, tumor size, TNM staging, histological type,tumor infiltration depth and presence or absence of lymphatic metastasis, but CXCR4 and CD133 co-expressionwas associated with TNM staging and lymphatic metastasis. The 3-year survival rate of patients with CXCR4and CD133 co-expression was 27.3% (3/11), and that of the remainderwas 76.3% (29/38), the difference beingsignificant (χ2=7.0206, p=0.0081). Conclusions: CXCR4 and CD133 co-expression may be a risk factor for poorprognosis of patients with stage Ⅱ~Ⅲ colon cancer.     

The expression of CXCL12 and CXCR4 in gastric cancer and their correlation to lymph node metastasis

The purpose of this study was to investigate the expression of CXCL12 and its receptor CXCR4 in gastric cancer and to determine their relationship with lymph node metastasis. Fifty patients with pathologically confirmed gastric cancer were analyzed from September 2004 to December 2004. The expression levels of CXCL12 and CXCR4 were examined by immunohistochemical staining in the primary gastric tumor tissues, adjacent normal mucosa tissues, and metastatic lymph nodes and were analyzed along with clinicopathological risk factors, to determine their correlation with the prognosis. Positive staining for CXCL12 and CXCR4 was identified in 90.0 and 80.0% of the primary gastric tumor tissues, respectively, with significantly higher expression intensities observed in the primary gastric tumor tissues than in the adjacent normal mucosa tissues (P?<?0.01 and P?=?0.01, respectively). Positive staining for CXCL12 and CXCR4 was identified in 94.4 and 91.7% of metastatic lymph nodes, respectively, with significantly higher expression intensities in the metastatic lymph nodes than in the adjacent normal mucosa tissues (P?<?0.01 and P?=?0.01, respectively). Expression of CXCL12 in the primary gastric tumor tissues was not significantly associated with the clinicopathological characteristics of the tumor or the disease prognosis. However, the intensity of CXCR4 staining in primary tumor tissues was positively related with lymph node metastasis, TNM staging, and disease prognosis (P?=?0.04, 0.03, 0.03, respectively). CXCL12 and CXCR4 are related to formation of gastric tumors and lymph node metastasis. Furthermore, the expression of CXCR4 could be used as a biomarker to predict malignant features of gastric cancer.     

nm23 protein expression in colorectal carcinoma metastasis in regional lymph nodes and the liver.

AIMS: The nm23 gene has been shown to have metastasis suppressing activity and abnormalities of the gene or its expression may be important in tumour progression and dissemination. This study was set out to investigate the possible role of the nm23 in colorectal adenocarcinoma dissemination by examining the level of nm23 protein expression in colorectal carcinoma metastasis in regional lymph nodes and the liver. METHODS: Using a monoclonal antibody, NCL-nm23 (Novocastra), immunohistochemical expression of the nm23 protein was examined in cases of metastatic colorectal adenocarcinoma in regional lymph nodes (n=71) and liver (n=36). RESULTS: The cases of lymph-node metastasis also had tissues from the primary carcinoma (n=71) and matching normal non-neoplastic mucosal tissues (n=71) from the colon and rectum available for the study. More than half of the cases of primary colorectal carcinoma (43/71; 60%) displayed strong nm23 immunoreactivity, with a similar proportion of the lymph-node metastases (40/71 cases; 56%) having strong nm23 immunostaining. However, only a small minority of the normal controls of non-neoplastic colorectal epithelia (12/71 cases; 17%) had strong nm23 immunoreactivity. The difference in nm23 protein expression between normal colorectal mucosa and primary colorectal carcinoma was statistically significant (P=0.0001; chi-squared test with continuity correction). However, no significant difference in nm23 protein expression was found between primary colorectal carcinoma and lymph-node metastases (P=0.81; chi-squared test with continuity correction). Most of the liver metastases (24/36 cases; 67%) had strong nm23 immunostaining but this finding was not statistically significant when compared with that seen in primary colorectal carcinoma (P=0.62; chi-squared test with continuity correction). In addition, nm23 expression was not found to significantly correlate with 5-year survival of patients with liver metastasis (P=0.86), suggesting that it had no predictive value for overall patient survival. There was also no significant correlation between disease recurrence and nm23 expression (P=0.63). CONCLUSIONS: In summary, increased nm23 protein immunoreactivity is seen in the majority of colorectal carcinomas when compared to normal colorectal tissues but no significant difference in nm23 expression was found between primary colorectal carcinoma and metastatic carcinoma in regional lymph nodes or the liver. This study suggests that increased nm23 expression may be important in early colorectal carcinoma but not in later progression and dissemination of the tumour. In conclusion, the role and importance of the nm23 gene in the development of tumour metastasis in colorectal carcinoma is questionable. Copyright Harcourt Publishers Limited.     

胃癌及区域淋巴结CD44v6、nm23-H1表达与其病理特征及预后关系的研究

目的:探讨胃癌及其区域淋巴结CD44V6、nm23-H1表达与胃癌病理特征及预后的关系.方法:本研究采用SP免疫组织化学方法对110例胃癌及613枚区域淋巴结组织中的CD44V6、nm23-H1的表达进行检测.结果:在胃癌原发灶和在淋巴结转移灶,CD44V6阳性表达率分别为65.5%和89.4%,nm23-H1阳性表达率分别为39.1%和16.8%.CD44V6、nm23-H1表达率与胃癌的组织学类型、浸润深度、淋巴结转移密切相关.胃癌原发灶CD44V6阳性表达组5年生存率显著低于阴性表达组(P＜0.01);nm23-H1阳性表达组5年生存率显著高于阴性表达组(P＜0.01).结论:对胃癌组织进行CD44V6、nm23-H1蛋白的检测,有助于预测胃癌进程和淋巴结转移的诊断,以及评估胃癌患者的预后.     

胃癌和转移淋巴结组织ADAMTS1表达及其生物学意义的探讨

目的:探讨含(I)型血小板结合蛋白基序的解聚蛋白样金属蛋白酶( ADAMTS1)在胃癌及转移淋巴结组织中的表达,分析其与胃癌浸润深度、分化程度及淋巴结转移等临床病理学参数的关系.方法:免疫组化法检测72例成对胃癌组织、癌旁组织及胃周淋巴结组织标本ADAMTS1的表达,半定量评分系统评估染色,分析ADAMTS1表达与胃癌临床病理学参数的关系.结果:ADAMTS1在胃癌组织中弱阳性率、阳性率及强阳性率分别为37.5％(27/72)、4.2％(3/72)和1.4％(1/72),在癌旁组织中分别为58.3％(42/72)、25.0％(18/72)和11.1％(8/72),在转移淋巴结组织中分别为55.9％(33/59)、20.3％(12/59)和3.4％(2/59),在无转移淋巴结组织中分别为46.2％(6/13)、0(0/13)和0(0/13).胃癌组织ADAMTS1表达明显低于癌旁组织,z=-6.481,P＜0.000 1;转移淋巴结组织ADAMTS1表达明显高于胃癌组织(z=4.164,P＜0.000 1)和无转移淋巴结组织(z=2.130,P=0.033).ADAMTS1在有淋巴结转移的胃癌组织中表达明显高于无淋巴结转移的胃癌组织,z=2.045,P=0.041.结论:ADAMTS1在胃癌原发灶中呈现低表达,在转移淋巴结中呈现高表达.ADAMTS1在胃癌中表达与淋巴结转移有关,表明ADAMTS1基因表达在胃癌原发肿瘤生长及转移中可能存在不同的作用机制,可能与肿瘤微环境有关.     

Quantitative analysis of lymphangiogenic markers for predicting metastasis of human gastric carcinoma to lymph nodes

The spread of tumor cells to regional lymph nodes is an early event of gastric cancer metastasis. In our study, we assessed the expression of lymphangiogenic factors and lymphatic endothelial markers in gastric carcinoma tissues and compared expression levels with the status of lymph node metastasis. We also examined the correlation between lymphatic vessel density (LVD) in primary tumors and lymph node metastasis. Paired biopsy samples (tumor and corresponding normal mucosa) of gastric tissue were obtained from 39 patients with gastric carcinoma. The expression of VEGF-C, VEGF-D, VEGFR-3 and podoplanin mRNAs was assessed by real-time quantitative PCR. The expression of VEGF-C (but not of VEGF-D) was significantly greater in patients with lymph node metastasis than in those without metastasis. The expression of lymphatic endothelial markers VEGFR-3 and podoplanin was also significantly greater in the node-positive group. LVD, as assessed by immunohistochemistry for podoplanin, was correlated with lymph node metastasis. These results indicate that quantitative analysis of lymphangiogenic markers in gastric biopsy specimens may be useful in predicting metastasis of gastric cancer to regional lymph nodes.