本文關(guān)鍵詞： 喉鱗癌 免疫組織化學(xué) TGFβ1 TβRⅠ TβRⅡ Smad7　出處：《河北醫(yī)科大學(xué)》2010年碩士論文　論文類型：學(xué)位論文

【摘要】： 目的:喉癌是耳鼻咽喉-頭頸外科常見(jiàn)的惡性腫瘤之一。喉癌的發(fā)生、發(fā)展與其它惡性腫瘤一樣,可能與多因素引起相關(guān)基因表達(dá)水平的改變有關(guān)。TGFβ1信號(hào)轉(zhuǎn)導(dǎo)通路是正常的信號(hào)轉(zhuǎn)導(dǎo)通路,它的功能是調(diào)節(jié)細(xì)胞增殖、分化、轉(zhuǎn)移及凋亡,其基本過(guò)程是:TGFβ1通過(guò)其受體(TβRⅠ和TβRⅡ)和下游調(diào)節(jié)因子(Smads蛋白,包括受體調(diào)節(jié)型Smad和共同中介型Smad)起作用,而Smad7作為抑制性Smad,抑制TGFβ1介導(dǎo)的信號(hào)轉(zhuǎn)導(dǎo)。信號(hào)轉(zhuǎn)導(dǎo)通路中的因子表達(dá)紊亂,可促進(jìn)細(xì)胞的惡性化進(jìn)展。轉(zhuǎn)化生長(zhǎng)因子β1(transforming growth factorβ1, TGFβ1)是一種雙重功能的調(diào)節(jié)因子,尤其是對(duì)于腫瘤,在腫瘤的早期階段,抑制腫瘤細(xì)胞的增殖,以及使腫瘤細(xì)胞的信號(hào)轉(zhuǎn)導(dǎo)通路失活,被認(rèn)為對(duì)腫瘤的抑制作用;在腫瘤的晚期階段,則對(duì)腫瘤的促進(jìn)作用,通過(guò)刺激血管生成、免疫抑制及合成細(xì)胞外基質(zhì)而提供適宜腫瘤生長(zhǎng)、浸潤(rùn)和轉(zhuǎn)移的環(huán)境。本研究以喉鱗癌為研究對(duì)象,采用免疫組化方法,探討TGFβ1、TβRⅠ、TβRⅡ和Smad7信號(hào)轉(zhuǎn)導(dǎo)通路在喉鱗癌組織中的表達(dá),進(jìn)一步了解四種基因蛋白在喉鱗癌發(fā)生、發(fā)展、轉(zhuǎn)移中的作用以及它們的相互關(guān)系。 方法: 1應(yīng)用免疫組織化學(xué)(immunohistochemistr, IHC)S-P法檢測(cè)43例喉鱗癌組織和12例癌旁組織中TGFβ1、TβRⅠ、TβRⅡ和Smad7的蛋白表達(dá)情況。 2運(yùn)用統(tǒng)計(jì)軟件SPSS13.0對(duì)數(shù)據(jù)進(jìn)行統(tǒng)計(jì)分析。以P≤0.05為差異在統(tǒng)計(jì)學(xué)上有顯著性意義,P≤0.01為差異在統(tǒng)計(jì)學(xué)上有非常顯著性意義。 結(jié)果: 1癌和癌旁組織中TGFβ1的蛋白表達(dá)與臨床參數(shù)之間的關(guān)系喉鱗癌組織和癌旁組織中TGFβ1蛋白的表達(dá)強(qiáng)度相比差異在統(tǒng)計(jì)學(xué)有非常顯著性(P0.01),TGFβ1在喉癌組織中的陽(yáng)性表達(dá)率(74.42%)高于癌旁組織中的陽(yáng)性表達(dá)率(25.00%)。TGFβ1蛋白的表達(dá)與臨床分期有關(guān)(Ⅲ、Ⅳ期高于Ⅰ、Ⅱ期,P0.05);淋巴結(jié)轉(zhuǎn)移有關(guān)(轉(zhuǎn)移組高于非轉(zhuǎn)移組,P0.01);與病理分級(jí)有關(guān)(P0.05),而與年齡、性別、臨床分型無(wú)關(guān)(P0.05)。 2癌和癌旁組織中TβRⅠ的蛋白表達(dá)與臨床參數(shù)之間的關(guān)系喉鱗癌組織和癌旁組織中TβRⅠ蛋白的表達(dá)強(qiáng)度相比差異在統(tǒng)計(jì)學(xué)上無(wú)顯著性(P0.05),但TβRⅠ在喉癌組織中的陽(yáng)性表達(dá)率(32.56%)低于癌旁組織中的陽(yáng)性表達(dá)率(41.67%)。TβRⅠ蛋白的表達(dá)與臨床分期有關(guān)(Ⅲ、Ⅳ期的表達(dá)低于Ⅰ、Ⅱ期,P0.05);與淋巴結(jié)轉(zhuǎn)移有關(guān)(轉(zhuǎn)移組的表達(dá)低于非轉(zhuǎn)移組,P0.05),而與年齡、性別、臨床分型及病理分級(jí)無(wú)關(guān)(P0.05)。 3癌和癌旁組織中TβRⅡ的蛋白表達(dá)與臨床參數(shù)之間的關(guān)系喉鱗癌組織和癌旁組織中TβRⅡ蛋白的表達(dá)強(qiáng)度相比差異在統(tǒng)計(jì)學(xué)上有顯著性(P0.05),且陽(yáng)性表達(dá)率分別為39.53%和75.00%,TβRⅡ在喉鱗癌組織中的表達(dá)明顯低于癌旁組織。TβRⅡ的蛋白表達(dá)與臨床分期有關(guān)(Ⅲ、Ⅳ期的表達(dá)低于Ⅰ、Ⅱ期,P0.05);與淋巴結(jié)轉(zhuǎn)移有關(guān)(轉(zhuǎn)移組的表達(dá)低于非轉(zhuǎn)移組,P0.05),而與年齡、性別、臨床分型、病理分級(jí)無(wú)關(guān)(P0.05)。 4癌和癌旁組織中Smad7的蛋白表達(dá)與臨床參數(shù)之間的關(guān)系喉鱗癌組織和癌旁組織中Smad7蛋白的表達(dá)強(qiáng)度相比差異在統(tǒng)計(jì)學(xué)有顯著性(P0.01),且陽(yáng)性表達(dá)率分別為76.74%和8.33%,Smad7在喉鱗癌中的表達(dá)明顯高于癌旁組織。Smad7的蛋白表達(dá)與臨床分期有關(guān)(Ⅲ、Ⅳ期的表達(dá)高于Ⅰ、Ⅱ期,P0.01);與淋巴結(jié)轉(zhuǎn)移有關(guān)(轉(zhuǎn)移組的表達(dá)高于非轉(zhuǎn)移組,P0.05);與病理分級(jí)(P0.01)有關(guān),而與年齡、性別、臨床分型無(wú)關(guān)(P0.05)。 5 TGFβ1和TβRⅠ、TGFβ1和TβRⅡ、TGFβ1和Smad7表達(dá)的相關(guān)性在喉鱗癌組織中,TGFβ1蛋白陽(yáng)性表達(dá)率為74.42%,TβRⅠ蛋白陽(yáng)性表達(dá)率分別為32.56%,TβRⅡ蛋白陽(yáng)性表達(dá)率分別為39.53%,Smad7蛋白陽(yáng)性表達(dá)率為76.74%。TGFβ1與TβRⅠ的表達(dá)呈負(fù)相關(guān)(r=-0.503,P0.01);TGFβ1與TβRⅡ的表達(dá)呈負(fù)相關(guān)(r=-0.398,P0.01);TGFβ1與Smad7的表達(dá)呈正相關(guān)(r=0.434,P0.01)。 結(jié)論: 1 TGFβ1、TβRⅠ、TβRⅡ和Smad7基因蛋白在喉鱗癌組織及癌旁組織中均有表達(dá)。 2 TGFβ1和Smad7在喉鱗癌組織中的定性表達(dá)均高于癌旁組織,TβRⅠ和TβRⅡ在喉鱗癌組織中的定性表達(dá)均低于癌旁組織,提示四種基因可能與喉癌的發(fā)生有關(guān)。 3 TGFβ1、TβRⅠ、TβRⅡ和Smad7在喉鱗癌組織中的表達(dá)與臨床分期、淋巴結(jié)轉(zhuǎn)移有關(guān);TGFβ1和Smad7在喉鱗癌組織中的表達(dá)與病理分級(jí)有相關(guān)性,提示四種基因可能與喉鱗癌的發(fā)展及轉(zhuǎn)移有關(guān)。 4 TGFβ1和TβRⅠ、TGFβ1和TβRⅡ、TGFβ1和Smad7表達(dá)均相關(guān),說(shuō)明四種基因在TGFβ1信號(hào)轉(zhuǎn)導(dǎo)通路中相互作用,共同參與喉鱗癌的發(fā)生、發(fā)展及轉(zhuǎn)移有關(guān)。
[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.

【學(xué)位授予單位】：河北醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2010
【分類號(hào)】：R739.65

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