【摘要】：目的：鼻咽癌（Nasopharyngealcarcinoma,NPC）是我國(guó)最常見(jiàn)的頭頸部腫瘤。由于鼻咽癌發(fā)生部位隱蔽、早起癥狀輕微，約60%的病人在確診為鼻咽癌時(shí)已發(fā)生淋巴結(jié)轉(zhuǎn)移或遠(yuǎn)處轉(zhuǎn)移。因此，研究鼻咽癌的發(fā)生機(jī)制并尋找新的診斷和判斷分子標(biāo)記物具有重要意義。研究發(fā)現(xiàn)，F(xiàn)OXO3a轉(zhuǎn)錄因子和缺氧誘導(dǎo)因子HIF-1α在許多人類(lèi)腫瘤的發(fā)展和預(yù)后中起重要的作用。然后，其具體作用并不清楚。因此，，我們研究FOXO3a和HIF-1α在鼻咽癌中的表達(dá)水平和臨床意義，為鼻咽癌治療提供新的策略。 方法：應(yīng)用免疫組化、RT-PCR和Westernblot法檢測(cè)48例鼻咽癌組織和15例正常鼻咽粘膜組織中FOXO3a和HIF-1α的mRNA、蛋白的表達(dá)水平，分析FOXO3a和HIF-1α與各種臨床病理參數(shù)之間的關(guān)系。結(jié)果：FOXO3a蛋白在鼻咽癌組織中的表達(dá)率（50.0%）明顯低于 正常鼻咽粘膜組織中的表達(dá)率（80.0%），差異明顯，且統(tǒng)計(jì)學(xué)意義（P=0.006）。而HIF-1α蛋白在鼻咽癌中的表達(dá)率（75.0%）明顯高于正常鼻咽粘膜組織中的表達(dá)率（33.3%），差異有統(tǒng)計(jì)學(xué)意義（P=0.011）。FOXO3a蛋白的表達(dá)與鼻咽癌的臨床分期、T分期、淋巴結(jié)轉(zhuǎn)移、遠(yuǎn)處轉(zhuǎn)移密切相關(guān)（P0.05）,HIF-1α蛋白的表達(dá)與鼻咽癌的淋巴結(jié)轉(zhuǎn)移、遠(yuǎn)處轉(zhuǎn)移密切相關(guān)（P0.05）。FOXO3a和HIF-1αmRNA在鼻咽癌和正常鼻咽粘膜組織中的表達(dá)差異無(wú)統(tǒng)計(jì)學(xué)意義。Spearman相關(guān)分析結(jié)果顯示FOXO3a和HIF-1α蛋白的表達(dá)呈負(fù)相關(guān)（rs= 0.667,P0.001）。 結(jié)論：FOXO3a和HIF-1α的異常表達(dá)可能與鼻咽癌的腫瘤生成、發(fā)展過(guò)程有一定的聯(lián)系。FOXO3a和HIF-1α可能成為判斷鼻咽癌生物學(xué)行為的重要指標(biāo)。
[Abstract]:Objective: nasopharyngeal carcinoma (Nasopharyngealcarcinoma,NPC) is the most common head and neck tumor in China. Due to the occult location of nasopharyngeal carcinoma (NPC) and mild symptoms of early onset, about 60% of the patients had lymph node metastasis or distant metastasis at the time of diagnosis of nasopharyngeal carcinoma (NPC). Therefore, it is of great significance to study the pathogenesis of nasopharyngeal carcinoma and to find new molecular markers. It has been found that FOXO3a transcription factor and hypoxia inducible factor HIF-1 偽 play an important role in the development and prognosis of many human tumors. Then, its specific role is not clear. Therefore, we study the expression level and clinical significance of FOXO3a and HIF-1 偽 in nasopharyngeal carcinoma, and provide a new strategy for the treatment of nasopharyngeal carcinoma. Methods: the expression of mRNA, protein of FOXO3a and HIF-1 偽 in 48 cases of nasopharyngeal carcinoma and 15 cases of normal nasopharyngeal mucosa were detected by immunohistochemistry, RT-PCR and Westernblot methods. The relationship between FOXO3a and HIF-1 偽 and various clinicopathological parameters was analyzed. Results: the expression rate of FOXO3a protein in nasopharyngeal carcinoma (50. 0%) was significantly lower than that in normal nasopharyngeal mucosa (80. 0%), and the difference was statistically significant (P < 0. 006). The expression rate of HIF-1 偽 protein in nasopharyngeal carcinoma (75.0%) was significantly higher than that in normal nasopharyngeal mucosa (33.3%), and the difference was statistically significant (P < 0.011). The expression of FOXO3a protein was related to the clinical stage of nasopharyngeal carcinoma (NPC). T stage, lymph node metastasis and distant metastasis were closely correlated (P0.05). The expression of HIF-1 偽 protein was associated with lymph node metastasis of nasopharyngeal carcinoma. There was no significant difference in the expression of FOXO3a and HIF-1 偽 mRNA between nasopharyngeal carcinoma and normal nasopharyngeal mucosa. The results of Spearman correlation analysis showed that the expression of FOXO3a and HIF-1 偽 protein was negatively correlated with the expression of FOXO3a and FOXO3a in nasopharyngeal carcinoma (NPC) and normal nasopharyngeal mucosa (P < 0. 667, P < 0. 05). P0.001). Conclusion: the abnormal expression of FOXO3a and HIF-1 偽 may be related to the tumorigenesis and development of nasopharyngeal carcinoma. FOXO3a and HIF-1 偽 may be important markers to judge the biological behavior of nasopharyngeal carcinoma.
【學(xué)位授予單位】：重慶醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2012
【分類(lèi)號(hào)】：R739.63

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