ORAOV1、VEGF和MVD在食管鳞状细胞癌中的相关性研究

发布时间：2018-05-23 13:22

  本文选题：食管鳞状细胞癌 + ORAOV1　； 参考：《石河子大学》2017年硕士论文

【摘要】：目的:食管癌是世界上最常见的消化道恶性肿瘤之一,其中食管鳞状细胞癌(esophageal squamous cell carcinoma,ESCC)是其最常见的组织学类型。ORAOV1,即口腔癌过表达序列1(oral cancer overexpressed)位于人类肿瘤高频扩增区域染色体11q13区段上,在多种人类恶性肿瘤中存在有该基因的扩增及蛋白的过表达,并且与肿瘤的浸润和转移密切相关,被认为是新的候选癌基因。本研究通过免疫组织化学(免疫组化)方法检测ORAOV1、血管内皮生长因子(vascular endothelial growth factor,VEGF)以及微血管密度(microvascular density,MVD)三者在ESCC中的相关性,探讨ORAOV1基因在ESCC血管生成中的作用。方法:选取121例癌旁正常食管(距离肿瘤边缘5cm)、96例ELGIN(esophageal low-grade intraepithelial neoplasia)、53例EHGIN(esophageal high-grade intraepithelial neoplasia)和143例ESCC组织,应用免疫组化方法检测VEGF蛋白表达水平,以及采用CD31抗体标记血管内皮细胞,计数CD31+MVD,同时与本课题组前期在上述相同组织中检测的ORAOV1蛋白表达水平相结合,检测ORAOV1、VEGF和MVD在ESCC组织中的相关性。此外,通过体外细胞学实验采用PCR(polymerase chain reaction)技术检测ORAOV1和VEGF的相关性。结果:1、与ORAOV1蛋白表达情况相一致,正常食管、ELGIN、EHGIN和ESCC组织中VEGF蛋白表达水平(p0.001)和MVD值逐渐增加(p0.001)。2、ESCC组织中VEGF蛋白表达水平(p=0.002)和MVD值(p=0.033)随着ORAOV1蛋白表达的升高而逐渐增加,而且MVD值随着VEGF蛋白表达水平的升高而增大(p0.001)。3、ESCC组织中ORAOV1蛋白表达水平与VEGF蛋白表达水平(r=0.281,p=0.002)呈正相关,与MVD值(r=0.204,p=0.015)呈正相关,而且VEGF蛋白表达水平和MVD值也呈正相关(r=0.373,p0.001)。4、与ORAOV1蛋白表达情况相一致,VEGF蛋白表达水平(p0.001)和MVD值(p=0.013)在淋巴结转移的ESCC组织中明显高于无淋巴结转移的组织,而且VEGF蛋白表达水平在TNM分期Ⅲ/Ⅳ期组织中明显高于Ⅰ/Ⅱ期组织(p0.001)。5、ESCC细胞中沉默ORAOV1基因能够下调VEGF m RNA的表达。结论:ESCC组织中ORAOV1、VEGF和MVD三者之间呈明显正相关,而且ESCC细胞系中ORAOV1基因能够调控VEGF的表达,提示ESCC中过表达的ORAOV1可能是通过上调VEGF的表达促进肿瘤血管的生成,从而在ESCC肿瘤细胞浸润和转移中发挥重要的作用。
[Abstract]:Objective: esophageal cancer is one of the most common malignant tumors of digestive tract in the world. Esophageal squamous cell carcinoma (ESCC) is the most common histological type of esophageal squamous cell carcinoma. ORAOV1, the overexpression sequence 1(oral cancer overexsedsed, is located on the chromosomal 11q13 region of the high frequency amplification region of human tumors. It is considered as a new candidate oncogene for its amplification and overexpression in a variety of human malignant tumors, and is closely related to tumor invasion and metastasis. In order to explore the role of ORAOV1 gene in angiogenesis of ESCC, we detected the correlation of ORAOV1, vascular endothelial growth factor (VEGF) and microvascular density (MVD) in ESCC by immunohistochemical method. Methods: the expression of VEGF protein was detected by immunohistochemical method in 121 cases of adjacent normal esophagus (56 cases of ELGIN(esophageal low-grade intraepithelial neoplasia, 53 cases of EHGIN(esophageal high-grade intraepithelial neoplasia) and 143 cases of ESCC, and CD31 antibody was used to label vascular endothelial cells. The correlation between CD31 and MVD in ESCC tissues was detected by combining with the expression level of ORAOV1 protein detected in the same tissues. In addition, the correlation between ORAOV1 and VEGF was detected by in vitro cytology using PCR(polymerase chain reactionation technique. Results in line with the expression of ORAOV1 protein in normal esophagus, the expression level of VEGF protein in normal esophagus and ESCC increased gradually (P 0.001) and MVD values increased gradually (P 0.002) and MVD (p0.033) increased with the increase of ORAOV1 protein expression in EHGIN and ESCC tissues. Moreover, the MVD value increased with the increase of VEGF protein expression level, and the expression level of ORAOV1 protein was positively correlated with the VEGF protein expression level (r = 0.281) and MVD value (r = 0.204 ~ 0. 015), and the expression of ORAOV1 protein was positively correlated with the expression level of VEGF protein (r = 0. 281, P = 0. 002), and a positive correlation was found between the expression of ORAOV1 protein and the value of MVD. There was a positive correlation between the expression of VEGF protein and the value of MVD, which was consistent with the expression of ORAOV1 protein (p0.001) and MVD (0.013) in ESCC with lymph node metastasis, which was significantly higher than that in ESCC without lymph node metastasis. Moreover, the level of VEGF protein expression in stage 鈪，

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