發(fā)布時間：2018-05-23 13:22

  本文選題：食管鱗狀細胞癌 + ORAOV1��； 參考：《石河子大學》2017年碩士論文

【摘要】：目的:食管癌是世界上最常見的消化道惡性腫瘤之一,其中食管鱗狀細胞癌(esophageal squamous cell carcinoma,ESCC)是其最常見的組織學類型。ORAOV1,即口腔癌過表達序列1(oral cancer overexpressed)位于人類腫瘤高頻擴增區(qū)域染色體11q13區(qū)段上,在多種人類惡性腫瘤中存在有該基因的擴增及蛋白的過表達,并且與腫瘤的浸潤和轉(zhuǎn)移密切相關(guān),被認為是新的候選癌基因。本研究通過免疫組織化學(免疫組化)方法檢測ORAOV1、血管內(nèi)皮生長因子(vascular endothelial growth factor,VEGF)以及微血管密度(microvascular density,MVD)三者在ESCC中的相關(guān)性,探討ORAOV1基因在ESCC血管生成中的作用。方法:選取121例癌旁正常食管(距離腫瘤邊緣5cm)、96例ELGIN(esophageal low-grade intraepithelial neoplasia)、53例EHGIN(esophageal high-grade intraepithelial neoplasia)和143例ESCC組織,應(yīng)用免疫組化方法檢測VEGF蛋白表達水平,以及采用CD31抗體標記血管內(nèi)皮細胞,計數(shù)CD31+MVD,同時與本課題組前期在上述相同組織中檢測的ORAOV1蛋白表達水平相結(jié)合,檢測ORAOV1、VEGF和MVD在ESCC組織中的相關(guān)性。此外,通過體外細胞學實驗采用PCR(polymerase chain reaction)技術(shù)檢測ORAOV1和VEGF的相關(guān)性。結(jié)果:1、與ORAOV1蛋白表達情況相一致,正常食管、ELGIN、EHGIN和ESCC組織中VEGF蛋白表達水平(p0.001)和MVD值逐漸增加(p0.001)。2、ESCC組織中VEGF蛋白表達水平(p=0.002)和MVD值(p=0.033)隨著ORAOV1蛋白表達的升高而逐漸增加,而且MVD值隨著VEGF蛋白表達水平的升高而增大(p0.001)。3、ESCC組織中ORAOV1蛋白表達水平與VEGF蛋白表達水平(r=0.281,p=0.002)呈正相關(guān),與MVD值(r=0.204,p=0.015)呈正相關(guān),而且VEGF蛋白表達水平和MVD值也呈正相關(guān)(r=0.373,p0.001)。4、與ORAOV1蛋白表達情況相一致,VEGF蛋白表達水平(p0.001)和MVD值(p=0.013)在淋巴結(jié)轉(zhuǎn)移的ESCC組織中明顯高于無淋巴結(jié)轉(zhuǎn)移的組織,而且VEGF蛋白表達水平在TNM分期Ⅲ/Ⅳ期組織中明顯高于Ⅰ/Ⅱ期組織(p0.001)。5、ESCC細胞中沉默ORAOV1基因能夠下調(diào)VEGF m RNA的表達。結(jié)論:ESCC組織中ORAOV1、VEGF和MVD三者之間呈明顯正相關(guān),而且ESCC細胞系中ORAOV1基因能夠調(diào)控VEGF的表達,提示ESCC中過表達的ORAOV1可能是通過上調(diào)VEGF的表達促進腫瘤血管的生成,從而在ESCC腫瘤細胞浸潤和轉(zhuǎn)移中發(fā)揮重要的作用。
[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，

本文編號：1924900