本文關鍵詞：Hedgehog信號通路Gli家族成員在鼻咽癌的表達及其臨床意義　出處：《桂林醫(yī)學院》2016年碩士論文　論文類型：學位論文

  更多相關文章： 鼻咽癌 Sonic Hedgehog信號通路 Gli家族 PI3K/AKT Gli1 Gli2 Gli3

【摘要】：目的:研究Sonic Hedgehog信號通路核轉錄因子Gli1、Gli2、Gli3和PI3K/AKT信號通路核心分子Phosoho-AKT(P-AKT)在鼻咽癌組織中的表達及其潛在的臨床意義。分析Gli1、Gli2、Gli3、P-AKT蛋白表達水平之間的關系,并探討Hh信號通路與PI3K/AKT信號通路的關系。方法:收集2013.6~2015.6廣西壯族自治區(qū)南溪山醫(yī)院收治經病理診斷為鼻咽癌的60例患者的活檢鼻咽組織標本(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)為對照組。應用免疫組織化學技術檢測上述組織對Gli1、Gli2、Gli3及P-AKT蛋白的表達水平;染色結果根據腫瘤組織中染色細胞百分比和細胞染色強度進行評判,按染色細胞百分比評分:0%-5%(0分)、6%-25%(1分)、26%-50%(2分)、51%-75%(3分)、75%(4分);細胞染色強度評分:無染色(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分。對Hh信號通路成員Gli1、Gli2、Gli3蛋白表達水平進行分組,≤6為低表達組,得分≥7為高表達組。而將P-AKT綜合評分≥4定為陽性,4定為陰性。應用SPSS18.0軟件進行分析,鼻咽癌組及正常鼻咽黏膜上皮組間免疫反應評分均值的比較應用t檢驗;計數資料差異比較應用χ2檢驗;應用Spearman等級相關分析各蛋白表達水平的關系,以P0.05判定為差異具有統計學意義,比較Gli1、Gli2、Gli3及P-AKT蛋白表達水平與鼻咽癌患者臨床病理參數的關系。結果:Gli1、Gli2、Gli3及P-AKT蛋白定位于胞質或胞核,Gli1、Gli2及Gli3的陽性染色以癌細胞胞核為主,而P-AKT的陽性染色以癌細胞胞質為主。鼻咽癌組織對Gli1、Gli2、Gli3及P-AKT蛋白的表達明顯上調。鼻咽癌組織對Gli1、Gli2及Gli3表達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蛋白表達水平與淋巴結轉移相關(P0.05),Gli3與臨床病理參數的比較無統計學意義。P-AKT在鼻咽癌組織中表達水平高于正常鼻咽黏膜上皮(2.53±2.75vs0.53±0.92,P0.001),且與淋巴結是否轉移有關(P0.05),與其它臨床病理參數的比較無統計學意義(P0.05)。Gli1與Gli2、Gli3、P-AKT表達均呈顯著正相關(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表達均呈顯著正相關(分別為r=0.609,P0.001;r=0.416,P=0.001)。結論:Sonic Hedgehog信號通路核轉錄因子Gli1、Gli2、Gli3和PI3K/AKT通路核心分子P-AKT在鼻咽癌中均呈過度表達,且P-AKT蛋白水平分別與Gli1和Gli2表達呈顯著相關,提示Hh信號通路和PI3K/AKT通路在鼻咽癌發(fā)生發(fā)展過程起共同作用。
[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.

【學位授予單位】：桂林醫(yī)學院
【學位級別】：碩士
【學位授予年份】：2016
【分類號】：R739.63

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