本文關(guān)鍵詞：Hedgehog信號(hào)通路Gli家族成員在鼻咽癌的表達(dá)及其臨床意義　出處：《桂林醫(yī)學(xué)院》2016年碩士論文　論文類型：學(xué)位論文

  更多相關(guān)文章： 鼻咽癌 Sonic Hedgehog信號(hào)通路 Gli家族 PI3K/AKT Gli1 Gli2 Gli3

【摘要】：目的:研究Sonic Hedgehog信號(hào)通路核轉(zhuǎn)錄因子Gli1、Gli2、Gli3和PI3K/AKT信號(hào)通路核心分子Phosoho-AKT(P-AKT)在鼻咽癌組織中的表達(dá)及其潛在的臨床意義。分析Gli1、Gli2、Gli3、P-AKT蛋白表達(dá)水平之間的關(guān)系,并探討Hh信號(hào)通路與PI3K/AKT信號(hào)通路的關(guān)系。方法:收集2013.6~2015.6廣西壯族自治區(qū)南溪山醫(yī)院收治經(jīng)病理診斷為鼻咽癌的60例患者的活檢鼻咽組織標(biāo)本(存檔石蠟包埋組織),而且上述患者的臨床資料完整。另,選擇15例病理診斷為正常鼻咽黏膜上皮組織(存檔石蠟包埋組織)為對(duì)照組。應(yīng)用免疫組織化學(xué)技術(shù)檢測(cè)上述組織對(duì)Gli1、Gli2、Gli3及P-AKT蛋白的表達(dá)水平;染色結(jié)果根據(jù)腫瘤組織中染色細(xì)胞百分比和細(xì)胞染色強(qiáng)度進(jìn)行評(píng)判,按染色細(xì)胞百分比評(píng)分:0%-5%(0分)、6%-25%(1分)、26%-50%(2分)、51%-75%(3分)、75%(4分);細(xì)胞染色強(qiáng)度評(píng)分:無(wú)染色(0分)、淺黃色(1分)、棕色(2分)和深棕色(3分);兩者乘積為該蛋白綜合評(píng)分。對(duì)Hh信號(hào)通路成員Gli1、Gli2、Gli3蛋白表達(dá)水平進(jìn)行分組,≤6為低表達(dá)組,得分≥7為高表達(dá)組。而將P-AKT綜合評(píng)分≥4定為陽(yáng)性,4定為陰性。應(yīng)用SPSS18.0軟件進(jìn)行分析,鼻咽癌組及正常鼻咽黏膜上皮組間免疫反應(yīng)評(píng)分均值的比較應(yīng)用t檢驗(yàn);計(jì)數(shù)資料差異比較應(yīng)用χ2檢驗(yàn);應(yīng)用Spearman等級(jí)相關(guān)分析各蛋白表達(dá)水平的關(guān)系,以P0.05判定為差異具有統(tǒng)計(jì)學(xué)意義,比較Gli1、Gli2、Gli3及P-AKT蛋白表達(dá)水平與鼻咽癌患者臨床病理參數(shù)的關(guān)系。結(jié)果:Gli1、Gli2、Gli3及P-AKT蛋白定位于胞質(zhì)或胞核,Gli1、Gli2及Gli3的陽(yáng)性染色以癌細(xì)胞胞核為主,而P-AKT的陽(yáng)性染色以癌細(xì)胞胞質(zhì)為主。鼻咽癌組織對(duì)Gli1、Gli2、Gli3及P-AKT蛋白的表達(dá)明顯上調(diào)。鼻咽癌組織對(duì)Gli1、Gli2及Gli3表達(dá)水平均分別高于正常鼻咽黏膜上皮組織(6.35±3.87 vs 2.73±2.02,P0.001;5.70±4.13 vs 1.93±1.28,P0.001;6.07±3.60 vs 3.27±2.55,P=0.004),P0.05),Gli1、Gli2蛋白表達(dá)水平與淋巴結(jié)轉(zhuǎn)移相關(guān)(P0.05),Gli3與臨床病理參數(shù)的比較無(wú)統(tǒng)計(jì)學(xué)意義。P-AKT在鼻咽癌組織中表達(dá)水平高于正常鼻咽黏膜上皮(2.53±2.75vs0.53±0.92,P0.001),且與淋巴結(jié)是否轉(zhuǎn)移有關(guān)(P0.05),與其它臨床病理參數(shù)的比較無(wú)統(tǒng)計(jì)學(xué)意義(P0.05)。Gli1與Gli2、Gli3、P-AKT表達(dá)均呈顯著正相關(guān)(分別為r=0.380,P=0.003;r=0.313,P=0.015;r=0.284,P=0.028);Gli2與Gli3、P-AKT表達(dá)均呈顯著正相關(guān)(分別為r=0.609,P0.001;r=0.416,P=0.001)。結(jié)論:Sonic Hedgehog信號(hào)通路核轉(zhuǎn)錄因子Gli1、Gli2、Gli3和PI3K/AKT通路核心分子P-AKT在鼻咽癌中均呈過(guò)度表達(dá),且P-AKT蛋白水平分別與Gli1和Gli2表達(dá)呈顯著相關(guān),提示Hh信號(hào)通路和PI3K/AKT通路在鼻咽癌發(fā)生發(fā)展過(guò)程起共同作用。
[Abstract]:Objective: To study the Gli2 Sonic Hedgehog signal pathway of nuclear transcription factor Gli1, Gli3, and PI3K/AKT signal pathway of core molecule Phosoho-AKT (P-AKT) expression and clinical significance in nasopharyngeal carcinoma and its potential. The analysis of Gli1, Gli2, Gli3, the relationship between the expression level of P-AKT protein, and to explore the relationship between Hh signaling pathway and PI3K/AKT signaling pathway. Methods: collected from 2013.6~2015.6 the Guangxi Zhuang Autonomous Region Nanxi hill hospital diagnosed 60 cases of nasopharyngeal carcinoma patients with nasopharyngeal biopsy specimens (archived paraffin embedded tissue), and the patients with the clinical data of 15 cases of complete. On the other, pathological diagnosis of normal nasopharyngeal epithelial tissue (archived paraffin embedded tissue) as the control group. Gli2 immunohistochemistry was used to detect the organization of Gli1, the expression level of Gli3 and P-AKT protein staining in tumor tissue; according to the percentage of cells and staining Cell staining intensity evaluation score according to the percentage of cells staining: 0%-5% (0), 6%-25% (1), 26%-50% (2), 51%-75% (3), 75% (4); cell staining: no staining intensity score (0 points), yellow (1 points), brown (2 points) and dark brown (3); both the product of the protein composite score. Gli2 on Hh signaling pathway. The expression level of Gli3 protein, Gli1, were less than 6 for low expression group, scores of more than 7 high expression group. The P-AKT score is more than 4 as positive, 4 fixed negative. Analysis by SPSS18.0 software, compared with t test of nasopharyngeal carcinoma group and normal nasopharyngeal epithelia were immunoreactive score; count data were compared using 2 test; the expression of the protein by Spearman rank correlation analysis, the relationship between the levels of P0.05, to determine the differences were statistically significant, compared with Gli1, Gli2. The expression of Gli3 and P-AKT protein in nasopharyngeal carcinoma The relationship between the clinical pathological parameters of patients. Results: Gli1, Gli2, Gli3 and P-AKT protein located in the cytoplasm or nucleus, Gli1, Gli2 and Gli3 positive staining in nucleus of tumor cells, and P-AKT positive staining in the cytoplasm of cancer cells. Gli2 nasopharyngeal carcinoma on Gli1, and significantly up-regulated the expression of Gli3 and P-AKT protein. Gli1 of nasopharyngeal carcinoma, the expression level of Gli2 and Gli3 were significantly higher than in normal nasopharyngeal epithelial tissues (6.35 + 3.87 vs 2.73 + 2.02, P0.001; 5.70 + 4.13 vs 1.93 + 1.28, P0.001; 6.07 + 3.60 vs 3.27 + 2.55, P=0.004), P0.05, Gli1), the expression level of Gli2 protein transfer associated with lymph node (P0.05), Gli3 and clinical pathological parameters had no significant difference between the expression level is higher than that of normal nasopharyngeal epithelial.P-AKT in nasopharyngeal carcinoma (2.53 + 2.75vs0.53 + 0.92, P0.001), and lymph node metastasis (P0.05), and other clinical pathological parameters than With no statistical significance (P0.05).Gli1 and Gli2, Gli3, P-AKT expression showed a significant positive correlation (r=0.380, P=0.003; r=0.313, P=0.015; r=0.284, P=0.028); Gli2 and Gli3, P-AKT expression showed a significant positive correlation (r=0.609, P0.001; r=0.416, P=0.001). Conclusion: Sonic Hedgehog signal pathway of nuclear transcription factor Gli1, Gli2, Gli3 and PI3K/AKT P-AKT were the core molecular pathway is overexpressed in nasopharyngeal carcinoma, and P-AKT protein levels respectively with Gli1 and Gli2 expression were significantly correlated, suggesting that Hh signaling pathway and PI3K/AKT pathway in the occurrence and development of nasopharyngeal carcinoma may play an important role.

【學(xué)位授予單位】：桂林醫(yī)學(xué)院
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2016
【分類號(hào)】：R739.63

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