喉鳞癌组织中TGF-β1、TβRⅠ、TβRⅡ和Smad7表达及相关研究

发布时间：2018-01-25 21:18

本文关键词： 喉鳞癌免疫组织化学 TGFβ1 TβRⅠ TβRⅡ Smad7　出处：《河北医科大学》2010年硕士论文　论文类型：学位论文

【摘要】： 目的:喉癌是耳鼻咽喉-头颈外科常见的恶性肿瘤之一。喉癌的发生、发展与其它恶性肿瘤一样,可能与多因素引起相关基因表达水平的改变有关。TGFβ1信号转导通路是正常的信号转导通路,它的功能是调节细胞增殖、分化、转移及凋亡,其基本过程是:TGFβ1通过其受体(TβRⅠ和TβRⅡ)和下游调节因子(Smads蛋白,包括受体调节型Smad和共同中介型Smad)起作用,而Smad7作为抑制性Smad,抑制TGFβ1介导的信号转导。信号转导通路中的因子表达紊乱,可促进细胞的恶性化进展。转化生长因子β1(transforming growth factorβ1, TGFβ1)是一种双重功能的调节因子,尤其是对于肿瘤,在肿瘤的早期阶段,抑制肿瘤细胞的增殖,以及使肿瘤细胞的信号转导通路失活,被认为对肿瘤的抑制作用;在肿瘤的晚期阶段,则对肿瘤的促进作用,通过刺激血管生成、免疫抑制及合成细胞外基质而提供适宜肿瘤生长、浸润和转移的环境。本研究以喉鳞癌为研究对象,采用免疫组化方法,探讨TGFβ1、TβRⅠ、TβRⅡ和Smad7信号转导通路在喉鳞癌组织中的表达,进一步了解四种基因蛋白在喉鳞癌发生、发展、转移中的作用以及它们的相互关系。方法: 1应用免疫组织化学(immunohistochemistr, IHC)S-P法检测43例喉鳞癌组织和12例癌旁组织中TGFβ1、TβRⅠ、TβRⅡ和Smad7的蛋白表达情况。 2运用统计软件SPSS13.0对数据进行统计分析。以P≤0.05为差异在统计学上有显著性意义,P≤0.01为差异在统计学上有非常显著性意义。结果: 1癌和癌旁组织中TGFβ1的蛋白表达与临床参数之间的关系喉鳞癌组织和癌旁组织中TGFβ1蛋白的表达强度相比差异在统计学有非常显著性(P0.01),TGFβ1在喉癌组织中的阳性表达率(74.42%)高于癌旁组织中的阳性表达率(25.00%)。TGFβ1蛋白的表达与临床分期有关(Ⅲ、Ⅳ期高于Ⅰ、Ⅱ期,P0.05);淋巴结转移有关(转移组高于非转移组,P0.01);与病理分级有关(P0.05),而与年龄、性别、临床分型无关(P0.05)。 2癌和癌旁组织中TβRⅠ的蛋白表达与临床参数之间的关系喉鳞癌组织和癌旁组织中TβRⅠ蛋白的表达强度相比差异在统计学上无显著性(P0.05),但TβRⅠ在喉癌组织中的阳性表达率(32.56%)低于癌旁组织中的阳性表达率(41.67%)。TβRⅠ蛋白的表达与临床分期有关(Ⅲ、Ⅳ期的表达低于Ⅰ、Ⅱ期,P0.05);与淋巴结转移有关(转移组的表达低于非转移组,P0.05),而与年龄、性别、临床分型及病理分级无关(P0.05)。 3癌和癌旁组织中TβRⅡ的蛋白表达与临床参数之间的关系喉鳞癌组织和癌旁组织中TβRⅡ蛋白的表达强度相比差异在统计学上有显著性(P0.05),且阳性表达率分别为39.53%和75.00%,TβRⅡ在喉鳞癌组织中的表达明显低于癌旁组织。TβRⅡ的蛋白表达与临床分期有关(Ⅲ、Ⅳ期的表达低于Ⅰ、Ⅱ期,P0.05);与淋巴结转移有关(转移组的表达低于非转移组,P0.05),而与年龄、性别、临床分型、病理分级无关(P0.05)。 4癌和癌旁组织中Smad7的蛋白表达与临床参数之间的关系喉鳞癌组织和癌旁组织中Smad7蛋白的表达强度相比差异在统计学有显著性(P0.01),且阳性表达率分别为76.74%和8.33%,Smad7在喉鳞癌中的表达明显高于癌旁组织。Smad7的蛋白表达与临床分期有关(Ⅲ、Ⅳ期的表达高于Ⅰ、Ⅱ期,P0.01);与淋巴结转移有关(转移组的表达高于非转移组,P0.05);与病理分级(P0.01)有关,而与年龄、性别、临床分型无关(P0.05)。 5 TGFβ1和TβRⅠ、TGFβ1和TβRⅡ、TGFβ1和Smad7表达的相关性在喉鳞癌组织中,TGFβ1蛋白阳性表达率为74.42%,TβRⅠ蛋白阳性表达率分别为32.56%,TβRⅡ蛋白阳性表达率分别为39.53%,Smad7蛋白阳性表达率为76.74%。TGFβ1与TβRⅠ的表达呈负相关(r=-0.503,P0.01);TGFβ1与TβRⅡ的表达呈负相关(r=-0.398,P0.01);TGFβ1与Smad7的表达呈正相关(r=0.434,P0.01)。结论: 1 TGFβ1、TβRⅠ、TβRⅡ和Smad7基因蛋白在喉鳞癌组织及癌旁组织中均有表达。 2 TGFβ1和Smad7在喉鳞癌组织中的定性表达均高于癌旁组织,TβRⅠ和TβRⅡ在喉鳞癌组织中的定性表达均低于癌旁组织,提示四种基因可能与喉癌的发生有关。 3 TGFβ1、TβRⅠ、TβRⅡ和Smad7在喉鳞癌组织中的表达与临床分期、淋巴结转移有关;TGFβ1和Smad7在喉鳞癌组织中的表达与病理分级有相关性,提示四种基因可能与喉鳞癌的发展及转移有关。 4 TGFβ1和TβRⅠ、TGFβ1和TβRⅡ、TGFβ1和Smad7表达均相关,说明四种基因在TGFβ1信号转导通路中相互作用,共同参与喉鳞癌的发生、发展及转移有关。
[Abstract]:Objective: laryngeal carcinoma is one of the most common otorhinolaryngology malignant tumors. Tumorigenesis, development as well as other malignant tumors, may cause the expression of related genes related to.TGF beta and 1 multi factor signal transduction pathway of signal transduction pathway is normal, its function is to regulate cell proliferation, differentiation, metastasis and apoptosis, the basic process is: TGF beta 1 through its receptor (T beta R beta R I and T II) and downstream factor (Smads protein, including receptor regulation of type Smad and type Smad common intermediary role, and Smad7) as inhibitory Smad, inhibition of signal transduction mediated by TGF beta 1. Factor signal transduction pathway expression in malignant disorders, progress can promote the cell. Transforming growth factor beta 1 (transforming growth factor TGF beta 1, beta 1) is a regulator of a dual function, especially for tumors in the early stage of tumor, inhibition of tumor cell The proliferation of tumor cells and the signal transduction pathway inactivation is thought to inhibit tumor; in the late stage of tumor, the tumor promoting effect by stimulating angiogenesis, immune suppression and synthesis of extracellular matrix and provide appropriate tumor growth, invasion and metastasis of laryngeal squamous cell carcinoma in this study environment. As the research object, using immunohistochemical methods to investigate TGF beta 1 beta T, R I, the expression of T beta R II and Smad7 signal transduction pathway in laryngeal squamous cell carcinoma, to further understand, four kinds of gene protein in laryngeal squamous cell carcinoma metastasis for development, and the relations among them.
Method:
1 the expression of TGF beta 1, T beta R I, T T R II and Smad7 in 43 cases of laryngeal squamous cell carcinoma and 12 cases of adjacent tissues were detected by immunohistochemistr (IHC) S-P.
2 using statistical software SPSS13.0 statistical analysis of data. The P is less than or equal to 0.05 there was a significant difference in statistics, P is less than or equal to 0.01 there was a significant difference in statistics.
Result:
1 in carcinoma and adjacent tissue protein TGF beta 1 expression intensity of tissue and clinical parameters in the relationship between laryngeal squamous cell carcinoma and adjacent TGF beta 1 protein compared to a significant difference in Statistics (P0.01), TGF beta 1 in laryngeal carcinoma positive expression rate (74.42%) higher than the positive expression of cancer in the adjacent tissues (25%) was significantly related with the clinical staging of.TGF beta 1 protein (III, IV than I, II, P0.05); lymph node metastasis (metastasis group than in non metastasis group, P0.01); related to pathological grading (P0.05), but not with age, sex, clinical type independent (P0.05).
2 cancer and T beta R I protein expression intensity of T beta R 1 protein organization and the relationship between the clinical parameters of laryngeal squamous cell carcinoma and adjacent carcinoma compared no significant difference in Statistics (P0.05), but the positive expression of T beta R 1 in laryngeal carcinoma rate (32.56%) the positive expression rate of lower than that of the adjacent tissues (41.67%) expression of.T beta R 1 protein and clinical stage (III, IV expression is lower than that of I, II, P0.05); associated with lymph node metastasis (expression of metastasis group was lower than that in non metastasis group, P0.05), but not with age, gender, clinical classification and pathology independent (P0.05).
3 cancer and T beta R II protein expression intensity of T beta R II protein and clinical parameters of the relationship between laryngeal squamous cell carcinoma tissues and the differences were statistically significant (P0.05), and the positive rates were 39.53% and 75%, the protein expression and clinical T beta R II expression in laryngeal squamous cell carcinoma tissues was significantly lower than that in adjacent tissues of.T beta R II stage (III, IV expression is lower than that of I, II, P0.05); associated with lymph node metastasis (expression of metastasis group was lower than that in non metastasis group, P0.05), but not with age, gender, clinical regardless of type, pathological grade (P0.05).
The expression of Smad7 4 in carcinoma and adjacent tissue protein expression Smad7 tissue and clinical parameters in the relationship between laryngeal squamous cell carcinoma tissues and the differences were statistically significant (P0.01), and the positive rates were 76.74% and 8.33%, the protein expression and clinical expression of Smad7 in laryngeal squamous cell carcinoma was obviously higher than the adjacent tissues.Smad7 stage (III, IV expression is higher than that of I, II, P0.01); associated with lymph node metastasis (expression of metastasis group was higher than that in non metastasis group, P0.05); and the pathological grade (P0.01), but not with age, sex, clinical type independent (P0.05).
5 TGF beta 1 and beta T R 1, TGF beta 1 and T beta R II, TGF beta 1 and Smad7 expression correlation in laryngeal squamous cell carcinoma, the positive expression of TGF protein beta 1 rate was 74.42%, the positive expression of T beta protein 1 R rate was 32.56%, the positive expression of T beta R II protein respectively. 39.53%, the positive expression rate of Smad7 protein expression of 76.74%.TGF beta 1 and beta T R I was negatively correlated (r=-0.503, P0.01); expression of TGF was negatively correlated with T beta 1 beta R II (r=-0.398, P0.01); the expression of TGF was positively related to beta 1 and Smad7 (r=0.434, P0.01).
Conclusion:
1 TGF beta 1, T beta R I, T beta R II and Smad7 gene protein were expressed in the tissues of laryngeal squamous cell carcinoma and in the para cancerous tissues.
The qualitative expression of 2 TGF 1 and Smad7 in laryngeal squamous cell carcinoma tissues were higher than those in adjacent tissues. The qualitative expression of T R R and T R II in laryngeal squamous cell carcinoma tissues were lower than those in adjacent tissues, suggesting that the four genes may be related to laryngeal carcinomas.
The expression of 3 TGF beta 1, T beta R I, T beta R II and Smad7 in laryngeal squamous cell carcinoma is related to the clinical stage and lymph node metastasis. The expression of TGF 1 and Smad7 in laryngeal squamous cell carcinoma is correlated with pathological grading, suggesting that four genes may be related to the development and metastasis of laryngeal squamous cell carcinoma.
4, TGF beta 1 and T beta R 1, TGF beta 1 and T beta R II, TGF TGF 1 and Smad7 expression are all correlated, indicating that four genes interact in the TGF beta 1 signal transduction pathway and participate in the occurrence, development and metastasis of laryngeal squamous cell 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】：2010
【分类号】：R739.65

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