本文選題：5T4 + CXCR4�。� 參考：《第四軍醫(yī)大學(xué)》2014年碩士論文

【摘要】：腎細(xì)胞癌（renal cell carcinoma，RCC）是泌尿系統(tǒng)中常見的惡性腫瘤，組織學(xué)類型以腎透明細(xì)胞癌（clear cell renal cell carcinoma，CCRCC）最為多見，約占85%以上。腎細(xì)胞癌早期癥狀不明顯，生長隱匿，進(jìn)展迅速，易有化療抵抗，且缺乏特異性的檢測和評估因子，晚期多有遠(yuǎn)位轉(zhuǎn)移�；趯δI透明細(xì)胞癌浸潤和轉(zhuǎn)移機(jī)制的探索，我們選擇了與腫瘤細(xì)胞分化、粘附、遷移、運動相關(guān)的5T4和CXCR4進(jìn)行研究。5T4（5T4oncofetal trophoblast glycoprotein）為胚胎滋養(yǎng)層糖蛋白，在早期胚胎中高表達(dá)于滋養(yǎng)層細(xì)胞，而胎盤以外的正常成熟組織很少表達(dá)，后來研究發(fā)現(xiàn)其在人體部分實體腫瘤中也有較高表達(dá)，并推測5T4在腫瘤中的高表達(dá)，能使腫瘤細(xì)胞表現(xiàn)出與滋養(yǎng)層細(xì)胞相似的浸潤能力，導(dǎo)致腫瘤浸潤和轉(zhuǎn)移。CXCR4（CXC Chemokine receptor4，CXCR4）是趨化因子受體之一，，為趨化因子配體12（Chemokine CXC motifligand12，CXCL12）的受體，二者特異性的結(jié)合構(gòu)成了對人體生理、病理有重要作用的CXCL12/CXCR4生物軸，在腫瘤細(xì)胞侵潤和遷移過程中也發(fā)揮著重要作用。本實驗對5T4與CXCR4在腎透明細(xì)胞癌的表達(dá)進(jìn)行了定位、定性研究，探討二者在腎透明細(xì)胞癌中的表達(dá)與組織學(xué)病理分級、臨床分期之間的關(guān)系，結(jié)合免疫熒光雙標(biāo)方法，進(jìn)一步分析了二者的相關(guān)性。具體實驗設(shè)計如下： 目的：分析5T4和CXCR4在腎透明細(xì)胞癌中的表達(dá)及其與腎透明細(xì)胞癌臨床病理特征的關(guān)系，初步探討二者在腎透明細(xì)胞癌進(jìn)展過程中的作用關(guān)系。 方法：采用免疫組織化學(xué)方法檢測72例腎透明細(xì)胞癌及17例癌旁組織中5T4和CXCR4的表達(dá)，結(jié)合臨床分期和病理分級分析二者在腎透明細(xì)胞癌中的表達(dá)特點及相關(guān)性。采用免疫熒光雙標(biāo)技術(shù)對二者在腎透明細(xì)胞癌進(jìn)行共定位研究。 結(jié)果：腎透明細(xì)胞癌中5T4和CXCR4的表達(dá)明顯高于癌旁腎臟組織（P＜0.05），5T4的表達(dá)與腎透明細(xì)胞癌的病理分級、臨床分期呈正相關(guān)(P＜0.05)。CXCR4的表達(dá)與腎透明細(xì)胞癌的病理分級正相關(guān)（P=0.025），與臨床分期無顯著相關(guān)性（P=0.081）。二者的表達(dá)與患者的性別、年齡均無相關(guān)性（P＞0.05）。5T4與CXCR4在腎透明細(xì)胞癌病理分級中的表達(dá)率具有顯著線性關(guān)系（r=0.997，P＜0.01）。免疫熒光雙標(biāo)表明二者在腎透明細(xì)胞癌中存在共定位。 結(jié)論：①5T4與CXCR4在腎透明細(xì)胞癌中均有明顯表達(dá)，二者與腫瘤的病理組織學(xué)分級有關(guān)，可以用于判斷腎腫瘤的惡性程度。5T4與腎透明細(xì)胞癌的臨床分期相關(guān)，也可用于腎癌預(yù)后的評估；②5T4與CXCR4在癌旁組織腎小管上皮中的高表達(dá)與腎腫瘤細(xì)胞的發(fā)生、發(fā)展有密切關(guān)系，說明癌旁腎小管上皮細(xì)胞的惡性表型早于形態(tài)學(xué)變化；③在腎透明細(xì)胞癌中，5T4與CXCR4的表達(dá)不僅顯示了統(tǒng)計學(xué)的相關(guān)性，共定位研究也顯示了二者明顯的共表達(dá)與定位一致性，說明5T4與CXCR4在腎透明細(xì)胞癌的發(fā)生、發(fā)展過程中有重要的協(xié)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.
【學(xué)位授予單位】：第四軍醫(yī)大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2014
【分類號】：R737.11

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