肿瘤血管生成有关因子CD105、Galectin-3、EphA2和其配体EphrinA1在喉癌中的表达及评价

发布时间：2018-02-28 11:15

本文关键词： 喉鳞状细胞癌免疫组化肿瘤血管生成微血管密度转移复发预后 CD105 Galectin-3 EphA2 EphrinA1　出处：《广州医学院》2011年硕士论文　论文类型：学位论文

【摘要】：目的喉癌的发病率有逐年增加的趋势。关于喉癌发病相关因素的深入探究,以期早期发现、准确诊断、良好治疗,一直是研究追求的目标。近年来不少研究表明,恶性肿瘤的生长、转移呈血管依赖性,新生血管不但为恶性肿瘤的生长提供了充足的养分、排泄代谢废物,还为肿瘤细胞的转移提供了良好的通道。肿瘤血管的生成在恶性肿瘤的发生、发展、侵袭、转移及复发中,起着重要的作用。CD105、Galectin-3、EphA2和其配体EphrinA1蛋白等参与肿瘤内血管生成,在恶性肿瘤的生物学行为中起作用。但关于这些因素在喉癌中作用的研究,还不多见。本课题探讨CD105、Galectin-3、EphA2和其配体EphrinA1蛋白在喉癌发病机制中的作用、病理学价值、在喉癌的诊断、治疗、预后中的应用意义,并为喉癌抗血管生成治疗提供实验依据。方法标本均来自广州医学院附属广州市第一人民医院耳鼻咽喉科2000年1月至2004年6月期间,住院手术患者的常规石蜡包埋组织。本课题从分子水平,应用CD105单克隆抗体、Galectin-3单克隆抗体、EphA2多克隆抗体及EphrinA1多克隆抗体,采用免疫组化技术,检测CD105、Galectin-3、EphA2、EphrinA1蛋白在喉癌组织中的表达,计算CD105标染的微血管密度(MVD),分析该四种蛋白之间的相关性、对生存的影响。应用SPSS统计软件包(17.0)对各项结果进行统计学分析。结果 1 76例喉癌组织中以CD105标记的MVD为10.33±2.29,25例喉正常粘膜中MVD为1.20±1.04,两组比较,其差异有显著性意义(P0.05)。CD105-MVD的表达差异与喉癌的组织学分级、T分期、临床分期、颈淋巴结转移有关(P0.05);肿瘤复发与MVD有明显相关性,MVD与预后相关。 2 Galectin-3蛋白表达的阳性率在喉癌组织中为86.84%(66/76),在喉正常粘膜中为36%(9/25),其差异有显著性意义(P0.05)。Galectin-3蛋白表达与喉癌的T分期、临床分期、颈淋巴结转移有关(P0.05);肿瘤复发与Galectin-3有明显相关性,Galectin-3与预后相关。 3 EphA2、EphrinA1表达于肿瘤细胞的细胞浆/胞膜,其阳性率分别为78.95%(60/76)、81.85%(62/76),喉正常粘膜中的阳性表达率分别为40%(10/25)、44%(11/25),其差异有显著性意义(P0.05)。EphA2蛋白表达与肿瘤部位、组织学分级、T分期、临床分期、淋巴结转移有关。EphrinA1蛋白表达与肿瘤T分期、临床分期、颈淋巴结转移有关(P0.05),肿瘤复发与EphA2、EphrinA1有明显相关性,EphA2、EphrinA1与预后相关。 4 CD105、Galectin-3、EphA2和EphrinA1蛋白四者两两之间,均呈明显的正相关。 5生存分析显示喉癌患者总生存期随着CD105微血管计数的增高和Galectin-3、EphA2和EphrinA1染色级别的增高,而逐渐下降,其差异有显著性(P0.05)。Cox Regression综合生存分析显示,CD105、Galectin-3、EphA2同生存期相关,肿瘤分型、淋巴结转移、TNM分期、有无复发是患者预后独立的影响因素。结论 1 CD105与肿瘤活性血管生成有密切联系,是肿瘤新生血管的标志;肿瘤血管生成有利于肿瘤的侵袭、转移或复发。 2 Galectin-3的高表达与喉癌的发生密切相关,Galectin-3在喉肿瘤血管新生、喉癌的浸润、转移、预后中起作用。 3 EphA2、EphrinA1在喉癌中呈高表达;EphA2蛋白高表达与肿瘤部位、组织学分级、T分期、临床分期、淋巴结转移有关;EphrinA1蛋白的高表达与肿瘤T分期、临床分期、颈淋巴结转移有关;EphA2与EphrinA1的表达呈正相关,EphrinA1蛋白表达随着EphA2蛋白表达的增大而增大;EphA2、EphrinA1可能在喉癌的发生发展中起促进作用;EphA2、EphrinA1的高表达还可能提示了喉癌的恶性程度。 4喉癌中CD105、Galectin-3、EphA2和EphrinA1蛋白四者两两之间,均呈正相关,四者的协同作用促进了喉癌的发生、发展。 5生存分析显示CD105、Galectin-3、EphA2和EphrinA1蛋白的高表达与喉癌患者的生存较差有关,提示四者具有潜在的预后价值。 6对CD105标记的MVD、Galectin-3、EphA2及EphrinA1的检测,有助于喉癌的诊断;可作为判断喉癌侵袭、转移及预后的指标;并为喉癌的抗血管生成基因治疗提供实验依据。
[Abstract]:Purpose The incidence of laryngeal cancer has been increasing year by year . In order to find out early , accurate diagnosis and good treatment , it has been the goal of research . Tumor angiogenesis plays an important role in the development , development , invasion , metastasis and recurrence of malignant tumor . CD105 , Galectin - 3 , EphA2 and its ligand EphrinA1 protein play an important role in the development , invasion , metastasis and recurrence of malignant tumors . The purpose of this study was to investigate the role of CD105 , Galectin - 3 , EphA2 and its ligand EphrinA1 in the pathogenesis of laryngeal cancer . method The expression of CD105 , Galectin - 3 , EphA2 , EphA2 polyclonal antibody and EphrinA1 polyclonal antibody were detected by immunohistochemistry . The correlation between CD105 , Galectin - 3 , EphA2 and EphrinA1 in laryngeal cancer tissues was analyzed . Results The MVD of CD105 - MVD was 10.33 卤 2.29 , MVD was 1.20 卤 1.04 in 25 normal mucosa ( P0.05 ) . The expression of CD105 - MVD was correlated with histological grade , T stage , clinical stage and cervical lymph node metastasis ( P0.05 ) . The expression of Galectin - 3 protein was 86.84 % ( 66 / 76 ) in laryngeal carcinoma and 36 % ( 9 / 25 ) in normal mucosa . The expression of Galectin - 3 was related to T stage , clinical stage and cervical lymph node metastasis ( P0.05 ) . EphA2 and EphrinA1 were expressed in tumor cells . The positive rates were 78.95 % ( 60 / 76 ) , 81.85 % ( 62 / 76 ) , 40 % ( 10 / 25 ) and 44 % ( 11 / 25 ) respectively . EphA2 protein expression was related to tumor site , histological grade , T stage , clinical stage and lymph node metastasis . 4 CD105 , Galectin - 3 , EphA2 and EphrinA1 were positively correlated . Survival analysis showed that the overall survival time of patients with laryngeal cancer increased with the increase of CD105 microvessels counts and the increase of Galectin - 3 , EphA2 and EphrinA1 staining levels , and the difference was significant ( P0.05 ) . Cox regression analysis showed that CD105 , Galectin - 3 , EphA2 were related to survival , tumor typing , lymph node metastasis , TNM staging , and whether recurrence was an independent prognostic factor . Conclusion 1 CD105 is closely related to the angiogenesis of tumor , which is the marker of tumor neovascularization ; tumor angiogenesis is beneficial to invasion , metastasis or recurrence of tumor . The high expression of Galectin - 3 is closely related to the occurrence of laryngeal cancer , and Galectin - 3 plays a role in the invasion , metastasis and prognosis of laryngeal tumor angiogenesis and laryngeal carcinoma . EphA2 and EphrinA1 are related to the expression of EphA2 and EphrinA1 . EphA2 and EphrinA1 may play a role in the development of laryngeal cancer ; EphA2 , EphrinA1 may also promote the malignancy of laryngeal cancer . There were positive correlation between CD105 , Galectin - 3 , EphA2 and EphrinA1 protein in laryngeal carcinoma . 5 Survival analysis showed that high expression of CD105 , Galectin - 3 , EphA2 and EphrinA1 was associated with poor survival in patients with laryngeal cancer , suggesting that four patients had a potential prognostic value . 6 The detection of MVD , Galectin - 3 , EphA2 and EphrinA1 marked by CD105 can help the diagnosis of laryngeal cancer . It can be used as an index to judge the invasion , metastasis and prognosis of laryngeal cancer . It can provide experimental basis for the anti - angiogenic gene therapy of laryngeal cancer .

【学位授予单位】：广州医学院
【学位级别】：硕士
【学位授予年份】：2011
【分类号】：R739.65

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