Expression of wisp-1 and its significance in human colon cancer tissue

目的 探讨wisp-1在原发性结肠癌组织中的表达及临床意义.方法 应用免疫组化EnVision两步法检测wisp-1蛋白在138例结肠癌组织(48例含癌旁组织)、37例结肠腺瘤组织及66例结肠正常黏膜组织中的表达;应用实时荧光定量PCR检测wisp-1基因在37例新鲜原发性结肠肿瘤标本及对照组37例正常结肠中的表达;分析wisp-1蛋白、基因表达与患者临床病理特征的关系.结果 wisp-1蛋白在正常结肠、结肠腺瘤、癌旁组织及结肠癌中阳性率分别为53.0%、67.6%、75.0%、76.1%,其在结肠癌及癌旁组织中表达高于正常结肠(P<0.05);wisp-1蛋白表达与淋巴结转移及浸润深度有关(P<0.05);wisp-1基因在结肠肿瘤中平均表达是正常结肠中的1.349倍(P>0.05).结论 wisp-1蛋白异常可能在结肠癌的发生过程中起重要作用,而其基因在结肠癌中的作用尚需进一步研究.     

结肠腺瘤癌变过程中MTA1、RECK的表达及意义

目的分析MTA1、RECK在结肠腺瘤及结肠癌组织中的表达,探讨MTA1、RECK在结肠腺瘤癌变过程中的作用。方法应用免疫组化SABC法检测104例结肠癌组织、114例结肠腺瘤组织、30例正常结肠组织中MTA1、RECK蛋白表达,并复习相关文献。结果正常结肠组织、管状腺瘤、绒毛状腺瘤至结肠癌组织中MTA1的阳性率呈逐渐增高趋势(P0.05);结肠腺瘤(中重度异型增生)组中MTA1的阳性率高于结肠腺瘤(轻度异型增生)组(P0.05);MTA1在结肠癌中的阳性率随肿瘤临床Dukes分期的提高、淋巴结转移及肿瘤分化程度的降低而升高(P0.05)。RECK在正常结肠组织、管状腺瘤、绒毛状腺瘤、结肠癌组中的阳性率分别为100%、78.57%、77.27%、53.85%;正常结肠组织、管状腺瘤、绒毛状腺瘤至结肠癌组中RECK的阳性率呈逐渐降低趋势;中重度异型增生结肠腺瘤组中RECK的阳性率明显低于轻度异型增生结肠腺瘤组,差异有统计学意义(P0.05);RECK在结肠癌中的阳性率随肿瘤临床Dukes分期的提高、淋巴结转移及肿瘤分化程度的降低而降低(P0.05)。结论结肠癌组织中MTA1呈高表达,RECK表达缺失。MTA1、RECK参与正常组织、癌前病变、癌组织的发生、发展,在结肠腺瘤的癌变过程中起着重要作用。     

p38γMAPK蛋白在结肠癌组织中的表达及临床意义

目的探讨人结肠癌中p38γMAPK蛋白的表达及其临床意义。方法应用免疫组织化学法检测54例结肠癌组织、近癌旁组织、癌周正常组织和15例腺瘤息肉组织中p38γ蛋白的表达情况。结果p38γ蛋白的表达主要定位于胞质中,仅少量在胞核中表达。p38γ蛋白在结肠癌组织、癌旁组织、癌周正常组织中的高表达率分别为75.93%、51.85%、37.04%,在结肠腺瘤息肉组织中高表达率为33.33%。p38γ蛋白在结肠癌中的表达明显高于癌旁组织、癌周正常组织和腺瘤息肉组织,有统计学意义（P〈0.01）。p38γ的表达与Duke分期,组织分化程度及有无淋巴结转移有显著差异（P〈0.01）,p38γ的表达与年龄、性别、肿瘤大小、肿瘤位置无明显相关（P〉0.05）。结论结肠癌组织中p38γ蛋白处于过度表达状态,与结肠癌的发生、发展和转移密切相关。     

Kiss-1及基质金属蛋白酶9在结肠癌组织中的表达及意义

目的 检测Kiss-1及基质金属蛋白酶9(MMP-9)在结肠癌组织中的表达,探讨其临床意义.方法 采用链霉菌抗生物素蛋白-过氧化酶连接(SP)法检测68例结肠癌,26例结肠腺瘤及26例正常结肠组织中Kiss-1及MMP-9的表达情况,分析其与各种临床病理参数的关系及两者表达的关联性.结果 Kiss-1蛋白metastin在结肠癌组中的表达率(48.5%)明显低于结肠腺瘤组(80.8%)及正常结肠组(96.2%),并且其在结肠癌组中的表达率在不同的组织学分级、肌层浸润深度及淋巴结转移中差异有统计学意义(P均＜0.05).MMP-9在结肠癌组中的表达率(75%)明显高于结肠腺瘤组(38.5%)和正常结肠组(15.4%),其在结肠癌组中的表达率在不同的肌层浸润深度、淋巴转移中差异有统计学意义(P均＜0.05).Kiss-1蛋白metastin与MMP-9在结肠癌中的表达呈相反的趋势,有关联性(P＜0.01).结论 Kiss-1蛋白metastin的表达下调和MMP-9的表达上调可能与结肠癌的浸润、转移有关.     

Kiss-1及基质金属蛋白酶9在结肠癌组织中的表达及意义

目的检测Kiss-1及基质金属蛋白酶9(MMP-9)在结肠癌组织中的表达,探讨其临床意义。方法采用链霉菌抗生物素蛋白-过氧化酶连接(SP)法检测68例结肠癌,26例结肠腺瘤及26例正常结肠组织中Kiss-1及MMP-9的表达情况,分析其与各种临床病理参数的关系及两者表达的关联性。结果Kiss-1蛋白metastin在结肠癌组中的表达率(48.5%)明显低于结肠腺瘤组(80.8%)及正常结肠组(96.2%),并且其在结肠癌组中的表达率在不同的组织学分级、肌层浸润深度及淋巴结转移中差异有统计学意义(P均<0.05)。MMP-9在结肠癌组中的表达率(75%)明显高于结肠腺瘤组(38.5%)和正常结肠组(15.4%),其在结肠癌组中的表达率在不同的肌层浸润深度、淋巴转移中差异有统计学意义(P均<0.05)。Kiss-1蛋白metastin与MMP-9在结肠癌中的表达呈相反的趋势,有关联性(P<0.01)。结论Kiss-1蛋白metastin的表达下调和MMP-9的表达上调可能与结肠癌的浸润、转移有关。     

Tpl-2表达与结直肠癌发生发展的关系及意义

目的: 研究Tpl-2在结直肠癌旁正常黏膜、结直肠腺瘤以及结直肠腺癌中的蛋白表达情况,及其与结直肠癌临床病理参数的关系,探讨Tpl-2在结直肠癌发生发展中的意义。方法: 使用组织芯片及免疫组化方法检测Tpl-2在结直肠正常黏膜、腺瘤、癌组织中的表达情况,分析Tpl-2表达与结直肠癌的临床病理参数的相关性。结果: 24例癌旁正常黏膜中,Tpl-2低表达20例(83.3%)、高表达为4例(16.7%);24例腺瘤组织中Tpl-2低表达17例(70.8%)、高表达7例(29.2%);96例癌组织中Tpl-2低表达31例(32.3%)、高表达65例(67.7%)。与正常和腺瘤比较,癌组织Tpl-2表达均明显增高(P<0.01)。腺瘤和正常黏膜中Tpl-2表达无显著差异(P>0.05)。在96例结直肠癌组织中,Tpl-2表达与N分期、TNM分期相关(P<0.05),与性别、年龄、身高体重指数(BMI)、肿瘤大小、分化程度、T分期、M分期以及K-ras基因突变状况无明显相关(P>0.05)。结论: Tpl-2与结直肠癌发生及疾病进展具有较密切的关系,可能是一个促癌因子。     

结肠癌组织中SRSF1蛋白的表达及其临床意义

目的 探讨SRSF1在结肠癌中的表达及其与临床病理特征、预后的关系。方法 应用癌症基因组图谱(TCGA)和GEO数据库分析SRSF1 mRNA在结肠癌、正常结肠组织中的表达。采用免疫组化法检测SRSF1蛋白在94例结肠癌和86例癌旁正常组织中的表达,分析其表达与结肠癌临床病理特征的关系。应用Kaplan-Meier生存法分析SRSF1蛋白表达与结肠癌患者生存时间的相关性;采用Cox回归模型分析SRSF1在结肠癌风险预测中的评估价值。结果 TCGA和GEO数据库结果显示SRSF1 mRNA在结肠癌中高表达(P<0.05)。免疫组化检测显示SRSF1蛋白在结肠癌组织中的阳性率和高表达率分别为92.6%(87/94)和67.0%(63/94),显著高于癌旁正常组织(57.0%、11.6%)。χ²检验结果显示SRSF1表达水平与结肠癌患者临床分期相关(P=0.028)。Kaplan-Meier生存分析表明：SRSF1蛋白高表达结肠癌患者的总生存期低于SRSF1蛋白低表达患者(P=0.040)。Cox单因素回归分析表明：淋巴结转移(HR:3.638,95%CI=1.9...     

结肠癌组织中CDC6的表达及临床意义

目的探讨结肠癌组织中CDC6的表达及其临床意义。方法采用免疫组化MaxVision法检测121例结肠癌及癌旁正常黏膜组织中CDC6的表达,分析CDC6与结肠癌临床病理特征及预后的关系。结果CDC6在93.39%(113/121)的结肠癌组织中呈细胞核和细胞质阳性,仅在5.79%(7/121)的癌旁正常黏膜组织中呈细胞核阳性,差异有统计学意义(P<0.01)。CDC6表达升高与肿瘤转移、TNM分期明显相关(P<0.05);与患者年龄、性别、肿瘤分级等无关(P>0.05)。CDC6高表达组结肠癌患者5年生存率为54.9%(28/51),而低表达组为81.82%(18/22),差异有统计学意义(P<0.05)。结论CDC6在结肠癌组织中表达增高与癌转移、TNM分期及患者生存期相关,其有望成为结肠癌预后的可靠指标。     

乳腺癌中p16INK4a和视网膜母细胞瘤基因甲基化状况及其表达

目的 研究乳腺癌及癌旁增生组织中p16INK4a和视网膜母细胞瘤(RB)基因启动子区域的甲基化状况,并探讨基因异常甲基化与蛋白表达及其临床意义.方法 采用甲基化特异性PCR方法 对46例乳腺癌、22例癌旁增生组织及7例正常乳腺组织中p16INK4a和RB基因启动子区域甲基化状况进行检测,并采用免疫组织化学SP法对p16INK4a蛋白表达情况进行相应检测.结果 乳腺癌、癌旁增生组织和正常乳腺组织中p16INK4a基因的甲基化率分别为23.9%(11/46)、18.2%(4/22)、1/7;RB基因的甲基化率分别为10.8%(5/46)、9.1%(2/22)、0(0/7);肿瘤组织、癌旁增生组织和正常乳腺组织中p16INK4a基因、RB基因甲基化率差异均无统计学意义(P>0.05).正常乳腺组织、癌旁增生组织、乳腺癌中p16INK4a蛋白表达阳性率分别为7/7、60.8%(28/46)和81.8%(18/22),三者之间差异无统计学意义(P>0.05);肿瘤组织中p16INK4a蛋白表达与肿瘤分级相关(P<0.05);肿瘤组织中p16INK4a甲基化状况与其蛋白表达、肿瘤分级、ER表达阴性具有相关性(P<0.05),与肿瘤大小、淋巴结转移、年龄均不相关;RB基因甲基化状态与肿瘤分级、肿瘤大小、ER表达及年龄均无相关性,但与淋巴结转移相关(P<0.05).结论 p16INK4a基因异常甲基化可能在乳腺癌发生过程中作用有限,但在肿瘤的演进中发挥作用;RB基因甲基化检测对于分析乳腺癌进展及预后情况可能有一定参考价值;p16INK4a基因甲基化是p16INK4a蛋白失表达的机制之一.     

乳腺癌中p16INK4a和视网膜母细胞瘤基因甲基化状况及其表达

目的 研究乳腺癌及癌旁增生组织中p16INK4a和视网膜母细胞瘤(RB)基因启动子区域的甲基化状况,并探讨基因异常甲基化与蛋白表达及其临床意义.方法 采用甲基化特异性PCR方法 对46例乳腺癌、22例癌旁增生组织及7例正常乳腺组织中p16INK4a和RB基因启动子区域甲基化状况进行检测,并采用免疫组织化学SP法对p16INK4a蛋白表达情况进行相应检测.结果 乳腺癌、癌旁增生组织和正常乳腺组织中p16INK4a基因的甲基化率分别为23.9%(11/46)、18.2%(4/22)、1/7;RB基因的甲基化率分别为10.8%(5/46)、9.1%(2/22)、0(0/7);肿瘤组织、癌旁增生组织和正常乳腺组织中p16INK4a基因、RB基因甲基化率差异均无统计学意义(P>0.05).正常乳腺组织、癌旁增生组织、乳腺癌中p16INK4a蛋白表达阳性率分别为7/7、60.8%(28/46)和81.8%(18/22),三者之间差异无统计学意义(P>0.05);肿瘤组织中p16INK4a蛋白表达与肿瘤分级相关(P<0.05);肿瘤组织中p16INK4a甲基化状况与其蛋白表达、肿瘤分级、ER表达阴性具有相关性(P<0.05),与肿瘤大小、淋巴结转移、年龄均不相关;RB基因甲基化状态与肿瘤分级、肿瘤大小、ER表达及年龄均无相关性,但与淋巴结转移相关(P<0.05).结论 p16INK4a基因异常甲基化可能在乳腺癌发生过程中作用有限,但在肿瘤的演进中发挥作用;RB基因甲基化检测对于分析乳腺癌进展及预后情况可能有一定参考价值;p16INK4a基因甲基化是p16INK4a蛋白失表达的机制之一.     

Clinical significance and prognostic value of Nek2 protein expression in colon cancer

Objective: To determine the expression of NIMA-related kinase NEK2 and evaluate its clinical value in colon cancer. Method: Sixty specimens of colon cancer, 30 specimens of paracancerous colon tissues and 10 specimens of normal colon tissues conventionally resected in surgery at the Second Affiliated Hospital of Nantong University from February 2006 to February 2014 were collected. These tissues were detected for the expression of Nek2 using Western Blot and immunohistochemical staining. The relationship between Nek2 protein expression and the clinicopathology and prognosis of colon tissues was discussed. Results: The expression level and positive expression rate of Nek2 protein in the colon cancer were obviously higher than that in the paracancerous tissues and normal colon tissues. They were also significantly higher in the paracancerous tissues than in the normal tissues (P<0.05). Statistical analysis revealed that Nek2 protein expression was not obviously correlated with gender, age and tumor size, but obviously correlated with degree of differentiation (P=0.008), TNM staging (P=0.000), lymph node metastasis (P=0.022) and tumor invasion (P=0.011). With the plotting of Kaplan-Meier survival curve, it could be seen that Nek2 protein expression was not significantly correlated with survival (P=0.0048). High Nek2 protein expression may be an independent risk factor for colon cancer (HR=0.227, 95% CI 0.101-0.510). Conclusion: High Nek2 protein expression reflects the malignant behavior of colon cancer. Playing important roles in the occurrence of colon cancer, Nek2 protein expression has diagnostic and prognostic value in colon cancer.     

胃癌中RORα蛋白的表达及临床病理意义

目的观察维甲酸相关孤核受体α(Retinoid acid receptor related Orphan Receptorα,RORα)蛋白在胃癌中的表达,探讨其与胃癌发生、发展的关系,为寻找胃癌肿瘤标记物提供一定的实验依据。方法应用组织芯片技术及免疫组化SP法检测90例胃癌组织、48例癌旁胃黏膜组织与22例正常胃黏膜组织中RORα的表达,研究RORα与胃癌发生、发展的关系。结果 RORα蛋白在胃癌组织中表达下调,正常胃黏膜、癌旁胃黏膜和胃癌组织中RORα蛋白阳性率分别为83.36%(19/22),56.25%(27/48)和24.44%(22/90),3者相比差异有显著性(P<0.05)。高分化腺癌、中分化腺癌、低分化腺癌、黏液腺癌和印戒细胞癌中,RORα阳性率分别为45.00%(9/20)、27.59%(8/29)、14.29%(3/21)、11.11%(1/9)和9.05%(1/11)。高分化腺癌RORα阳性率高于低分化腺癌(P<0.05)。结论 RORα蛋白下调与胃癌的发生、发展相关,且可能与胃癌的分化程度有关。     

Cancer testis antigen OY-TES-1 expression and serum immunogenicity in colorectal cancer: its relationship to clinicopathological parameters

Cancer testis (CT) antigens are attractive targets for cancer immunotherapy because their expression is restricted in normal germ line tissues but frequently detected in variety of tumors. OY-TES-1 is identified as a member of CT antigens. Current knowledge about OY-TES-1 expression in colorectal cancer (CRC) is solely based on mRNA analysis. None of previous researches has studied OY-TES-1 at protein level. In this study, OY-TES-1 polyclonal antibody was generated. The expression of OY-TES-1 mRNA and protein was detected by RT-PCR and immunohistochemistry in 60 CRC and paired adjacent non-tumor tissues, 24 colorectal adenoma and 3 normal colon tissues, respectively. Sera from 73 CRC patients were also tested for OY-TES-1 antibody by ELISA. Our results showed that the frequency of OY-TES-1 mRNA expression was statistically higher in CRC (73.3%, 44/60) than that in adjacent non-tumor tissue (55.0%, 33/60) and colorectal adenoma (45.8%, 11/24). For the first time, OY-TES-1 protein expression was found in (43.3%, 26/60) of CRC tissues, but absent in any of adjacent non-tumor and colorectal adenoma tissues. No OY-TES-1 expression was found in normal colon by either RT-PCR or immunohistochemistry. Furthermore, OY-TES-1 protein expression was correlated with tumor invasion stage (P=0.004) and histological grade (P=0.040). Anti-OY-TES-1 antibody was detected in (9.6%, 7/73) of CRC patients’ sera but not in 76 healthy donors. This finding demonstrates that OY-TES-1 is frequently expressed in CRC and is able to induce humoral immune response spontaneously in CRC patients, suggesting that it might be a promising immunotherapy target for CRC.     

Sonic hedgehog mRNA及其蛋白在大肠癌的表达及其临床意义

目的 探讨大肠癌中Hedgehog信号通路相关基因Sonic hedgehog(SHH)的表达及其临床意义.方法 应用RT-PCR及免疫组织化学法(Envison二步法)检测本院2008年12月至2009年4月收集的43例大肠癌组织和距离癌10 cm以上的癌旁组织的SHHmRNA及蛋白的表达情况,并与20例非肠癌患者的正常大肠组织对照,分析其与大肠癌患者临床和病理各变量的相关性.结果 凝胶成像分析显示阳性表达的样本SHH mRNA片段大小为280 bp,与理论值相符,未表达的样本则未见相应条带.大肠癌组织SHHmRNA表达阳性率为27.9%(12/43),与癌旁组织的18.6%(8/43)差异无统计学意义(P＞0.05),但均显著高于正常大肠黏膜的0%(0/20)(均P＜0.05).SHH mRNA在大肠癌组织的表达强度显著高于癌旁组织(P＜0.05),在正常大肠黏膜则未见其表达.免疫组织化学显示SHH蛋白在大肠癌组织和癌旁组织均有阳性表达,细胞膜及胞质内出现棕黄褐色颗粒,背景不着色;正常大肠黏膜阴性表达.SHH蛋白在大肠癌组织的表达阳性率显著高于正常大肠黏膜[25.6%(11/43)比0%(0/20),P＜0.05],在大肠癌组织与癌旁组织、癌旁组织与正常大肠黏膜的表达阳性率差异则无统计学意义(均P＞0.05).SHH蛋白的表达强度大肠癌组织＞癌旁组织＞正常大肠黏膜(均P＜0.05).大肠癌组织中的SHH mRNA和蛋白表达强度与患者的年龄、性别、临床分期、肿瘤部位、肿瘤浸润深度、病理分型等变量均无明显关系(均P＞0.05).结论 SHH mRNA和蛋白在大肠癌组织中表达显著增强,但与临床和病理各变量无关联.     

Colon cancer bears overexpression of OTUB1

ObjectiveOTUB1 is a member of deubiquitinating enzymes; however, its expression and function in colon cancer are still unclear. The present study aimed at investigating the expression of OTUB1 in colon cancer and the relationship between the expression and some clinicopathologic parameters.MethodsImmunohistochemistry and quantitative real-time PCR were carried out in selected colon cancer and normal mucosa tissues.ResultsThe expression of OTUB1 protein in the colon cancer was significantly higher than normal mucosa, and the OTUB1 mRNA in colon cancer was also 3.15-fold higher than the normal mucosa. The higher expression of OTUB1 in colon cancer was related with tumor size, differentiation and lymph node metastasis.ConclusionsOTUB1 may play an important role in colon cancer development and metastasis.     

Endoglin (CD105) expression in angiogenesis of colon cancer: analysis using tissue microarrays and comparison with other endothelial markers

Some markers of angiogenic endothelial cells are emerging as targets of cancer therapy. The present study compares the expression of CD105 with that of other endothelial markers in all tissue layers during the development of colon cancer. We immunohistochemically analyzed the expression of the colon adenoma–carcinoma sequence by endothelial cells using a panel of eight endothelial markers. We examined sections from endoscopic mucosal resection and surgical resection of tubular adenoma (n=31), carcinoma in adenoma (n=11), and adenocarcinoma (n=34). Cylindrical cores were punched out from donor paraffin blocks of normal mucosa adjacent to tumors, from tumor lesions of mucosa, submucosa, muscularis propria, subserosa, and serosa, and from lymph node metastases. CD31 (PECAM-1) was universally expressed in the blood vessels of adenoma–carcinoma lesions as well as in normal mucosal vessels (80–95%), with no significant differences. In contrast, cancer-associated blood vessels (up to 80%) and cancer cells themselves expressed high levels of CD105. In normal mucosa, CD105 was weakly expressed in endothelial cells of capillaries (≦21%), and significant differences in its expression in endothelial cells between the normal mucosa and adenoma, carcinoma in adenoma, and adenocarcinoma were found. Flt-1, Flk-1, transforming growth factor-β1, transforming growth factor-β receptor II, and CD44 were strongly expressed in the cancer cells but were not expressed in the blood vessels. Vascular endothelial growth factor was expressed at <30% in the blood vessels of adenoma, carcinoma in adenoma, and carcinoma. Moreover, this study provided evidence that CD105 was expressed exclusively in endothelial blood vessels by double immunostaining of CD105 and D2-40. The present study shows that de novo blood vessels of colon cancer specifically express CD105. These findings provide the basis for novel antiangiogenic cancer therapies.     

SEL1L基因在食管癌中的表达及意义

目的探讨SEL1L（human Sel-1-like）mRNA及其蛋白在食管癌组织中的表达及其临床意义。方法应用免疫组织化学SP法检测90例手术切除的食管鳞状细胞癌、35例距癌灶边缘5am以上切缘的正常黏膜、60例癌旁黏膜及20例内窥镜活检的食管鳞状上皮不典型增生组织中SEL1L蛋白的表达;运用原位分子杂交技术检测上述癌组织、正常黏膜、癌旁黏膜中SEL1L mRNA的表达。结果（1）SEL1L mRNA在食管鳞状细胞癌的表达率为80．0％（72／90）,较正常黏膜的14．3％（5／35）和癌旁黏膜的16．7％（10／60）高（P〈0．01）;SEL1L mRNA在有淋巴结转移组的表达阳性率为92．7％（38／41）比无淋巴结转移组69．4％（34／49）高（P〈0．01）。（2）SEL1L蛋白在鳞状细胞癌的表达阳性率为87．8％（79／90）,在鳞状上皮不典型增生中的表达阳性率为90．0％（18／20）。分别较正常黏膜的14．3％（5／35）和癌旁黏膜的13．3％（8／60）高（P〈0．01）。SEL1L蛋白表达与患者性别、年龄、肿瘤位置、大小、分化程度、浸润深度、淋巴结转移及临床分期均无明显相关性（P〉0．05）。（3）食管鳞状细胞癌组织中SEL1L mRNA和SEL1L蛋白的表达呈明显正相关（r=0．492,P〈0．01）。结论（1）SEL1L蛋白表达的调控主要在转录水平,SEL1L蛋白表达水平的升高主要是相应转录水平上调的结果。（2）SEL1L蛋白过表达可能是食管鳞状细胞癌发生的早期表现,SEL1L蛋白的检测可作为识别食管癌高风险患者的生物标记物。     

Expression of heparanase in normal, dysplastic, and neoplastic human colonic mucosa and stroma. Evidence for its role in colonic tumorigenesis

The human heparanase gene, an endo-beta-glucuronidase that cleaves heparan sulfate at specific intrachain sites, has recently been cloned and shown to function in tumor progression and metastatic spread. Antisense digoxigenin-labeled heparanase RNA probe and monoclonal anti-human heparanase antibodies were used to examine the expression of the heparanase gene and protein in normal, dysplastic, and neoplastic human colonic mucosa. To our knowledge, this is the first systematic study of heparanase expression in human colon cancer. Both the heparanase gene and protein were expressed at early stages of neoplasia, already at the stage of adenoma, but were practically not detected in the adjacent normal-looking colon epithelium. Gradually increasing expression of heparanase was evident as the cells progressed from severe dysplasia through well-differentiated to poorly differentiated colon carcinoma. Deeply invading colon carcinoma cells showed the highest levels of the heparanase mRNA and protein associated with expression of both the gene and enzyme by adjacent desmoplastic stromal fibroblasts. A high expression was also found in colon carcinoma metastases to lung, liver, and lymph nodes, as well as in the accompanying stromal fibroblasts. Moreover, extracts derived from tumor tissue expressed much higher levels of the heparanase protein and activity as compared to the normal colon tissue. In all specimens, the heparanase gene and protein exhibited the same pattern of expression. These results suggest a role of heparanase in colon cancer progression and may have both prognostic and therapeutic applications.     

结直肠癌nm23基因表达、突变与侵袭、转移的相关性

目的　探讨nm2 3基因异常表达及突变与结直肠癌侵袭、转移之间的关系。方法　应用免疫组化LDP法、流式细胞术、PCR SSCP法对 1 5 0例结直肠癌标本及正常黏膜组织和 1 6例大肠腺瘤分 3组进行nm2 3蛋白检测和基因突变的筛查。结果　①免疫组化发现 73例结直肠癌中nm2 3 H1蛋白表达水平低于正常黏膜组织和良性腺瘤 (P <0 0 0 1 ,P <0 0 0 1 ) ,转移癌表达低于原发癌 (P <0 0 0 1 ) ,结直肠癌nm2 3 H1蛋白表达与组织分化、肠壁浸润、Dukes分期、转移均密切相关 (P <0 0 0 1 ) ,低表达组术后预后差于高表达组 (P <0 0 0 1 ) ;②流式细胞术研究表明 ,nm2 3 H1蛋白在癌组织表达低于癌旁组织 ;在结直肠癌伴有转移 (3/ 1 4 )时其表达低于未发生转移者 (1 1 / 1 4 ) ;③nm2 3 H1基因第 2～ 5位外显子在 6 3例结直肠癌组织中未发现异常突变。结论　结直肠癌中nm2 3基因突变可能是小概率事件 ,在结直肠癌的侵袭、转移中不发挥主要作用 ,而nm2 3 H1蛋白表达降低则与结直肠癌的侵袭、转移有关 ,提示检测nm2 3蛋白表达是判断结直肠癌预后有价值的指标之一。     

PXMP4促进结直肠癌细胞增殖、迁移和侵袭

目的 探讨过氧化物酶体膜蛋白4(peroxisomal membrane protein 4,PXMP4)对结直肠癌细胞增殖、迁移和侵袭能力的影响.方法 采用生物信息学分析65例配对结直肠癌组织中PXMP4 mRNA的表达.应用免疫组化检测112例配对结直肠癌组织中PXMP4的表达,并进行临床病理相关分析;利用RT-P...