5T4与CXCR4在肾透明细胞癌中的表达及相关性研究

发布时间：2018-05-13 20:14

本文选题：5T4 + CXCR4　；参考：《第四军医大学》2014年硕士论文

【摘要】：肾细胞癌（renal cell carcinoma，RCC）是泌尿系统中常见的恶性肿瘤，组织学类型以肾透明细胞癌（clear cell renal cell carcinoma，CCRCC）最为多见，约占85%以上。肾细胞癌早期症状不明显，生长隐匿，进展迅速，易有化疗抵抗，且缺乏特异性的检测和评估因子，晚期多有远位转移。基于对肾透明细胞癌浸润和转移机制的探索，我们选择了与肿瘤细胞分化、粘附、迁移、运动相关的5T4和CXCR4进行研究。5T4（5T4oncofetal trophoblast glycoprotein）为胚胎滋养层糖蛋白，在早期胚胎中高表达于滋养层细胞，而胎盘以外的正常成熟组织很少表达，后来研究发现其在人体部分实体肿瘤中也有较高表达，并推测5T4在肿瘤中的高表达，能使肿瘤细胞表现出与滋养层细胞相似的浸润能力，导致肿瘤浸润和转移。CXCR4（CXC Chemokine receptor4，CXCR4）是趋化因子受体之一，，为趋化因子配体12（Chemokine CXC motifligand12，CXCL12）的受体，二者特异性的结合构成了对人体生理、病理有重要作用的CXCL12/CXCR4生物轴，在肿瘤细胞侵润和迁移过程中也发挥着重要作用。本实验对5T4与CXCR4在肾透明细胞癌的表达进行了定位、定性研究，探讨二者在肾透明细胞癌中的表达与组织学病理分级、临床分期之间的关系，结合免疫荧光双标方法，进一步分析了二者的相关性。具体实验设计如下：目的：分析5T4和CXCR4在肾透明细胞癌中的表达及其与肾透明细胞癌临床病理特征的关系，初步探讨二者在肾透明细胞癌进展过程中的作用关系。方法：采用免疫组织化学方法检测72例肾透明细胞癌及17例癌旁组织中5T4和CXCR4的表达，结合临床分期和病理分级分析二者在肾透明细胞癌中的表达特点及相关性。采用免疫荧光双标技术对二者在肾透明细胞癌进行共定位研究。结果：肾透明细胞癌中5T4和CXCR4的表达明显高于癌旁肾脏组织（P＜0.05），5T4的表达与肾透明细胞癌的病理分级、临床分期呈正相关(P＜0.05)。CXCR4的表达与肾透明细胞癌的病理分级正相关（P=0.025），与临床分期无显著相关性（P=0.081）。二者的表达与患者的性别、年龄均无相关性（P＞0.05）。5T4与CXCR4在肾透明细胞癌病理分级中的表达率具有显著线性关系（r=0.997，P＜0.01）。免疫荧光双标表明二者在肾透明细胞癌中存在共定位。结论：①5T4与CXCR4在肾透明细胞癌中均有明显表达，二者与肿瘤的病理组织学分级有关，可以用于判断肾肿瘤的恶性程度。5T4与肾透明细胞癌的临床分期相关，也可用于肾癌预后的评估；②5T4与CXCR4在癌旁组织肾小管上皮中的高表达与肾肿瘤细胞的发生、发展有密切关系，说明癌旁肾小管上皮细胞的恶性表型早于形态学变化；③在肾透明细胞癌中，5T4与CXCR4的表达不仅显示了统计学的相关性，共定位研究也显示了二者明显的共表达与定位一致性，说明5T4与CXCR4在肾透明细胞癌的发生、发展过程中有重要的协同作用。
[Abstract]:Renal cell carcinoma (cell) is a common malignant tumor in the urinary system. The most common histologic type is clear cell renal cell carcinoma (CCRCC), accounting for more than 85%. The early symptom of renal cell carcinoma is not obvious, the growth is concealed, the progress is rapid, easy to have the chemotherapeutic resistance, and lacks the specific detection and the appraisal factor, the late stage has the distant metastasis. In order to explore the mechanism of invasion and metastasis of renal clear cell carcinoma, we selected 5T4 and CXCR4, which are related to differentiation, adhesion, migration and movement of tumor cells, to study. 5T4 and 5T4oncofetal trophoblast glycoprotein were selected as trophoblastic glycoprotein. In early embryos, high expression was found in trophoblast cells, but rarely in normal mature tissues outside the placenta. Later, it was found that high expression of 5T4 was also found in some solid tumors of human body, and the high expression of 5T4 in human tumors was speculated. CXCR4CXCR4CXCR4 is one of chemokine receptors, which is the receptor of chemokine ligand 12(Chemokine CXC motif ligand 12 (CXCL12). Pathologically important CXCL12/CXCR4 axis also plays an important role in the invasion and migration of tumor cells. In this study, the expression of 5T4 and CXCR4 in renal clear cell carcinoma was studied qualitatively, and the relationship between the expression of 5T4 and CXCR4 in renal clear cell carcinoma, histological grade, clinical stage and immunofluorescence double labeling method was discussed. The correlation between them is further analyzed. The experimental design is as follows: Objective: to analyze the expression of 5T4 and CXCR4 in renal clear cell carcinoma (RCC) and its relationship with clinicopathological features of renal clear cell carcinoma (RCC) and to explore the role of them in the progression of renal clear cell carcinoma (RCC). Methods: immunohistochemical method was used to detect the expression of 5T4 and CXCR4 in 72 cases of renal clear cell carcinoma and 17 cases of adjacent tissues. Immunofluorescence double-labeling technique was used to study the co-localization of the two in renal clear cell carcinoma (RCC). Results: the expression of 5T4 and CXCR4 in renal clear cell carcinoma was significantly higher than that in adjacent renal tissue (P < 0.05) and the pathological grade of renal clear cell carcinoma. There was a positive correlation between the expression of P < 0.05).CXCR4 and the pathological grade of renal clear cell carcinoma (RCC), but there was no significant correlation with the clinical stage (P < 0. 081). There was no correlation between the expression of 0.05).5T4 and CXCR4 in the pathological grade of renal clear cell carcinoma (P < 0.01). Immunofluorescence double labeling showed that they were co-located in renal clear cell carcinoma. Conclusion both of them are expressed in clear cell renal carcinoma. They are related to the pathological grade of the tumor, and can be used to judge the malignancy of renal tumor. 5T4 is related to the clinical stage of renal clear cell carcinoma. It can also be used to evaluate the prognosis of renal cell carcinoma. The high expression of 25T4 and CXCR4 in renal tubule epithelium is closely related to the occurrence and development of renal tumor cells, indicating that the malignant phenotype of renal tubular epithelial cells is earlier than that of morphology. 3The expression of 5T4 and CXCR4 in renal clear cell carcinoma not only showed statistical correlation, but also showed obvious coexpression and localization consistency between them in co-localization study, indicating the occurrence of 5T4 and CXCR4 in renal clear cell carcinoma. There is an important synergy in the process of development.
【学位授予单位】：第四军医大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R737.11

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