Dvl与Wnt2在喉鳞状细胞癌中的表达及意义

发布时间：2018-04-09 15:21

本文选题：喉鳞状细胞癌　切入点：Dvl　出处：《河北医科大学》2017年硕士论文

【摘要】：目的:喉鳞状细胞癌是头颈部肿瘤中的常见的恶性病变,占头颈部肿瘤的13.9%,目前对于喉癌的研究较广,在蛋白、通路及各种方面的研究呈集中性,但是喉癌具体通过哪一个机制发生主要作用,目前还没有很确切的表述,喉癌的发生、发展是多个因素或途径同时作用造成的,近年信号通路方面的研究已成为喉癌发生、发展的研究热点,为喉癌的治疗寻找新的治疗靶点,为喉癌的预后提供参考指标。信号转导通路以Wnt/β-catenin通路为最典型,是和肿瘤关系密切的信号转导通路之一,其主要的表现模式为:当wnt信号被始动因子激活后,通过下游一系列蛋白的影响,使β-catenin的磷酸化抑制,降解减少,导致胞核内的β-catenin异常积聚,与胞核内的因子(TCF/LEF)结合后形成复合物,从而调控细胞的生长。Dvl和Wnt2是wnt信号通路的主要成员,位于整个信号转导通路的上游,两个蛋白在通路中的表达是wnt通路的在信号传递的关键环节,两个蛋白的表达异常,最终可导致β-catenin在胞浆内水平增高累积入核,与转录因子相互作用,诱发靶基因的转录,参考以往的文献Wnt/β-catenin通路的dvl和wnt2在食管癌、非细胞肺癌、脑胶质瘤、乳腺癌、结肠癌中均有异常的表达。本研究通过免疫组化法检测Dvl蛋白与Wnt2在喉鳞状细胞癌及癌症周边正常组织中的表达,探讨两个蛋白在年龄,发生部位,临床分期、转移情况、是否吸烟在癌症及周边的组织的表达水平,探讨Dvl蛋白与Wnt2在喉癌的表达情况及相关性,分析探讨Dvl与Wnt2在喉癌中的发病机制,为寻找新的治疗途径提供一个新思路。方法:1研究对象1.1石蜡标本的收集选取河北医科大学第四医院耳鼻喉-头颈外科2014年10月至2016年11月期间在河北医科大学第四医院住院的喉肿物手术患者,其中实验组为48例,经病理确定为鳞状细胞癌的患者,经证实病历资料采集证实此组患者选择在术前均未行放、化疗等治疗,年龄43~71岁,平均58岁,对照组为24例喉癌患者的癌旁正常粘膜组织,距离癌原发部位0.5厘米。使用免疫组织化学(immunohistochemistry,IHC)S-P法对实验组和对照组中的Dvl及Wnt2的表达情况进行检测。1.2所有实验数据结果均使用SPSS21.0软件进行统计学分析,采用χ2检验,P0.05为有统计学意义。结果:1 Dvl的表达结果Dvl蛋白的蛋白阳性表达均呈棕黄色或棕褐色,主要定位在细胞质中,大多呈弥漫性表达。Dvl的表达在喉癌组织中的阳性表达率(79.2%)明显高于癌旁正常组织的阳性表达率(33.3%),两组经检验比较有统计学意义(P0.05)。1.1 Dvl在低分化、中高分化病理分型的阳性表达率分别为89.4%,65.5%,说明Dvl的在癌组织的表达随着分化程度的降低而升高,经统计学分析差异有统计学意义(P0.05)。1.2 Dvl蛋白的表达和临床分期有相关性,临床分期Ⅰ+Ⅱ的阳性表达(57.1%)明显低于Ⅲ+Ⅳ的表达(85.5%),经统计学分析差异有统计学意义(P0.05)。1.3 Dvl蛋白表达在有淋巴结转移的癌症组织表达(84.6%),明显高于无淋巴结转移的表达(63.6%),经统计学分析差异有统计学意义(P0.05)。1.4 Dvl蛋白在喉癌组的表达与患者的年龄、性别无明显相关性(P0.05)。2 Wnt2表达结果2.1 Wnt2的阳性物质主要在细胞质,呈黄色或棕黄色颗粒。Wnt2在喉癌组织中的阳性表达(75.0%)明显高于癌旁组织的阳性表达(45.8%),两组经检验差异有统计学意义(P0.05)。2.2 Wnt2的表达在低分化及中高分化喉癌组织中的表达分别为84.20%,58.60%,患者分化程度越低,wnt2的阳性表达越高,相反分化程度高的表达阳性率偏低,经统计学分析差异有统计学意义(P0.05)。2.3 Wnt2的表达与临床分期有相关性,临床分期越晚,wnt2表达就越强,在Ⅲ、Ⅳ期的阳性表达率(80.0%)明显高于Ⅰ、Ⅱ期的阳性表达率(60.7%),经统计学分析差异有统计学意义(P0.05)。2.4 Wnt2在伴有淋巴转移的喉癌组织中的表达(84.6%)明显高于无淋巴转移的癌组织表达(59.1%),经统计学分析差异有统计学意义(P0.05)。3 Dvl与Wnt2表达之间的相关性Dvl与Wnt2在喉鳞状细胞癌中的表达相关性分析,两者的表达属于正相关关系(r=0.537,P0.001)。结论:1喉鳞状细胞癌组织中的Dvl和Wnt2的均有表达,但喉癌组织中的阳性表达率明显高于癌旁正常黏膜组织,提示两者可能参与喉癌的发生和发展,并激发癌组织的恶性程度和淋巴结转移。2喉癌组织中的Dvl表达与临床分期,分化程度和淋巴结转移都存在高表达,提示Dvl蛋白的高表达可能在喉癌的发展、浸润及转移中起重要的作用。3 Wnt2在喉癌的临床分期、分化程度和淋巴结转移中都有高表达,提示Wnt2蛋白可能促进喉癌的发展,并可能是喉鳞状细胞癌的特征性的标记物。4 Dvl蛋白与Wnt2蛋白在喉癌中的表达有正相关性,两者可能通过某一个机制在喉癌的发生及发展中起促进作用,为喉癌的靶向治疗提供了一个新的依据,但是是否能成为喉癌的新治疗方法还需临床进一步验证。
[Abstract]:Objective: laryngeal squamous cell carcinoma of head and neck cancer is the common malignant tumor of head and neck lesions, accounted for 13.9%, the laryngeal cancer research widely in protein research pathway and various aspects of concentration, but the specific mechanism of laryngeal carcinoma which one occurs mainly through, there is no exact statement and the occurrence of laryngeal carcinoma, development is caused by many factors or ways at the same time the recent research pathway has become a hot research and development of laryngeal carcinoma, and find new therapeutic targets for the treatment of laryngeal cancer, and provide reference index for the prognosis of laryngeal carcinoma. With Wnt/ beta -catenin pathway is a typical signal transduction pathway. Is one of the signal transduction pathway and is closely related to tumor, its main performance is: when the Wnt signal is the initiating factor after activation by the downstream effects of a series of protein, the beta inhibition of the phosphorylation of -catenin, degradation Decrease in cell beta abnormal accumulation of -catenin in the nucleus, and the nucleus factor (TCF/LEF) combined to form a complex, which can modulate the cell growth of.Dvl and Wnt2 are the main members of the Wnt signaling pathway, located upstream of the signal transduction pathway, the expression of the two proteins in the pathway is the Wnt pathway in the key link of signal transmission and expression of two protein abnormalities that may eventually lead to increased beta -catenin accumulated in the nuclear level in the cytoplasm, and the interaction of transcription factors, induced transcription of target genes, referring to the previous literature Wnt/ beta -catenin pathway of DVL and Wnt2 in esophageal carcinoma, non-small cell lung cancer, glioma. Breast cancer, the expression of abnormalities in colorectal cancer. The expression of this study by immunohistochemical detection of Dvl protein and Wnt2 in laryngeal squamous cell carcinoma and cancer adjacent normal tissues, to investigate the two proteins in the age of occurrence, clinical stage, turn Shift, smoking in cancer and the surrounding tissues the expression level of Dvl protein and Wnt2 expression in laryngeal carcinoma and correlation analysis, investigate the pathogenesis of Dvl and Wnt2 in laryngeal carcinoma and provide a new way to find new ways for treatment. Methods: 1 subjects 1.1 paraffin specimens collected from throat tumor surgery patients hospitalized in the fourth Hospital of Hebei Medical University, Hebei Medical University Fourth Hospital of Otolaryngology Head and neck surgery from October 2014 to November 2016 period, the experimental group was 48 cases, pathologically identified as squamous cell carcinoma patients confirmed by clinical data collection confirmed that this group of patients were treated in the choice of preoperative radiotherapy, chemotherapy and other treatment, age 43~71 the average age of 58 years old, and a control group of 24 cases of patients with laryngeal cancer adjacent normal mucosa, primary cancer site distance of 0.5 cm. Using immunohistochemistry (immunohistochemistry, IHC) S-P The expression of Dvl and Wnt2 in the experimental group and the control group in.1.2 were detected in all the experimental data were analyzed by the statistics software of SPSS21.0, using 2 test, P0.05 had statistical significance. Results: the expression of the 1 Dvl protein positive expression of Dvl protein were yellow or brown, mainly located in the cytoplasm in the most diffuse expression in laryngeal carcinoma.Dvl expression rate (79.2%) was significantly higher than that of the positive expression rate of normal tissues (33.3%), two groups tested were statistically significant (P0.05).1.1 Dvl in low differentiation, positive expression in differentiated pathological types respectively 89.4%, 65.5%, Dvl in cancer increased with a decrease in the degree of differentiation, there was significant difference between the expression of.1.2 (P0.05) and clinical stage of Dvl protein, clinical stage I + The positive expression of (57.1%) was significantly lower than the expression III + IV (85.5%), there was significant difference between the expression of.1.3 (P0.05) Dvl protein expression in lymph node metastasis of cancer tissue (84.6%), significantly higher than the expression without lymph node metastasis (63.6%), statistically significant difference (P0.05).1.4 expression of Dvl protein in laryngeal cancer patients with the age group, there was no significant correlation between gender (P0.05) positive material.2 Wnt2 expression results of 2.1 Wnt2 mainly in the cytoplasm, the positive expression of yellow or brown granules of.Wnt2 in laryngeal carcinoma (75%) was significantly higher than that of positive expression in adjacent tissue (45.8%) the two group, the difference had statistical significance (P0.05) expression of.2.2 Wnt2 expression in low differentiation and high differentiation of laryngeal carcinoma were 84.20%, 58.60%, with the lower degree of differentiation, the positive expression of Wnt2 was higher in the degree of differentiation The low positive rate of high expression, statistically significant difference (P0.05) expression and clinical stage..2.3 Wnt2, the later clinical stage, the expression of Wnt2 was stronger in stage III, the positive expression rate (80%) was significantly higher than that of I, II positive expression rate (60.7%), there was significant difference between the expression of.2.4 Wnt2 (P0.05) in lymph node metastasis in laryngeal carcinoma (84.6%) was significantly higher than those without lymph node metastasis the expression of cancer tissue (59.1%), statistically significant difference (P0.05) expression analysis of relationship between Dvl and Wnt2 between the expression of.3 and Wnt2 in Dvl laryngeal squamous cell carcinoma, the expression of both belong to positive correlation (r=0.537, P0.001). Conclusion: the expression of 1 laryngeal squamous cell carcinoma Dvl and Wnt2 were positive, but the table in laryngeal carcinoma was significantly higher than that of adjacent normal mucosa tissues, That they may participate in the occurrence and development of laryngeal carcinoma, and stimulate cancer malignant degree and lymph node metastasis and clinical expression of Dvl.2 in laryngeal squamous cell carcinoma staging, differentiation and lymph node metastasis are high expression, high expression of Dvl may be in the development of laryngeal cancer invasion and metastasis play an important role in.3 Wnt2 in laryngeal carcinoma clinical stage, differentiation and lymph node metastasis has a high expression, suggesting Wnt2 protein may promote the development of laryngeal carcinoma, and may be a positive correlation between the expression of laryngeal squamous cell carcinoma of the characteristic markers of.4 Dvl protein and Wnt2 protein in laryngeal carcinoma. They may pass through a mechanism role in the occurrence and development of laryngeal carcinoma, laryngeal cancer targeted therapy provides a new basis, but whether it can still need further clinical validation of new methods of treatment of laryngeal carcinoma.

【学位授予单位】：河北医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R739.65

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