Hedgehog信号通路Gli家族成员在鼻咽癌的表达及其临床意义

发布时间：2017-12-31 12:25

本文关键词：Hedgehog信号通路Gli家族成员在鼻咽癌的表达及其临床意义　出处：《桂林医学院》2016年硕士论文　论文类型：学位论文

【摘要】：目的:研究Sonic Hedgehog信号通路核转录因子Gli1、Gli2、Gli3和PI3K/AKT信号通路核心分子Phosoho-AKT(P-AKT)在鼻咽癌组织中的表达及其潜在的临床意义。分析Gli1、Gli2、Gli3、P-AKT蛋白表达水平之间的关系,并探讨Hh信号通路与PI3K/AKT信号通路的关系。方法:收集2013.6~2015.6广西壮族自治区南溪山医院收治经病理诊断为鼻咽癌的60例患者的活检鼻咽组织标本(存档石蜡包埋组织),而且上述患者的临床资料完整。另,选择15例病理诊断为正常鼻咽黏膜上皮组织(存档石蜡包埋组织)为对照组。应用免疫组织化学技术检测上述组织对Gli1、Gli2、Gli3及P-AKT蛋白的表达水平;染色结果根据肿瘤组织中染色细胞百分比和细胞染色强度进行评判,按染色细胞百分比评分:0%-5%(0分)、6%-25%(1分)、26%-50%(2分)、51%-75%(3分)、75%(4分);细胞染色强度评分:无染色(0分)、浅黄色(1分)、棕色(2分)和深棕色(3分);两者乘积为该蛋白综合评分。对Hh信号通路成员Gli1、Gli2、Gli3蛋白表达水平进行分组,≤6为低表达组,得分≥7为高表达组。而将P-AKT综合评分≥4定为阳性,4定为阴性。应用SPSS18.0软件进行分析,鼻咽癌组及正常鼻咽黏膜上皮组间免疫反应评分均值的比较应用t检验;计数资料差异比较应用χ2检验;应用Spearman等级相关分析各蛋白表达水平的关系,以P0.05判定为差异具有统计学意义,比较Gli1、Gli2、Gli3及P-AKT蛋白表达水平与鼻咽癌患者临床病理参数的关系。结果:Gli1、Gli2、Gli3及P-AKT蛋白定位于胞质或胞核,Gli1、Gli2及Gli3的阳性染色以癌细胞胞核为主,而P-AKT的阳性染色以癌细胞胞质为主。鼻咽癌组织对Gli1、Gli2、Gli3及P-AKT蛋白的表达明显上调。鼻咽癌组织对Gli1、Gli2及Gli3表达水平均分别高于正常鼻咽黏膜上皮组织(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蛋白表达水平与淋巴结转移相关(P0.05),Gli3与临床病理参数的比较无统计学意义。P-AKT在鼻咽癌组织中表达水平高于正常鼻咽黏膜上皮(2.53±2.75vs0.53±0.92,P0.001),且与淋巴结是否转移有关(P0.05),与其它临床病理参数的比较无统计学意义(P0.05)。Gli1与Gli2、Gli3、P-AKT表达均呈显著正相关(分别为r=0.380,P=0.003;r=0.313,P=0.015;r=0.284,P=0.028);Gli2与Gli3、P-AKT表达均呈显著正相关(分别为r=0.609,P0.001;r=0.416,P=0.001)。结论:Sonic Hedgehog信号通路核转录因子Gli1、Gli2、Gli3和PI3K/AKT通路核心分子P-AKT在鼻咽癌中均呈过度表达,且P-AKT蛋白水平分别与Gli1和Gli2表达呈显著相关,提示Hh信号通路和PI3K/AKT通路在鼻咽癌发生发展过程起共同作用。
[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.

【学位授予单位】：桂林医学院
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：R739.63

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