本文選題：喉鱗狀細(xì)胞癌　切入點(diǎn)：Dvl　出處：《河北醫(yī)科大學(xué)》2017年碩士論文

【摘要】：目的:喉鱗狀細(xì)胞癌是頭頸部腫瘤中的常見(jiàn)的惡性病變,占頭頸部腫瘤的13.9%,目前對(duì)于喉癌的研究較廣,在蛋白、通路及各種方面的研究呈集中性,但是喉癌具體通過(guò)哪一個(gè)機(jī)制發(fā)生主要作用,目前還沒(méi)有很確切的表述,喉癌的發(fā)生、發(fā)展是多個(gè)因素或途徑同時(shí)作用造成的,近年信號(hào)通路方面的研究已成為喉癌發(fā)生、發(fā)展的研究熱點(diǎn),為喉癌的治療尋找新的治療靶點(diǎn),為喉癌的預(yù)后提供參考指標(biāo)。信號(hào)轉(zhuǎn)導(dǎo)通路以Wnt/β-catenin通路為最典型,是和腫瘤關(guān)系密切的信號(hào)轉(zhuǎn)導(dǎo)通路之一,其主要的表現(xiàn)模式為:當(dāng)wnt信號(hào)被始動(dòng)因子激活后,通過(guò)下游一系列蛋白的影響,使β-catenin的磷酸化抑制,降解減少,導(dǎo)致胞核內(nèi)的β-catenin異常積聚,與胞核內(nèi)的因子(TCF/LEF)結(jié)合后形成復(fù)合物,從而調(diào)控細(xì)胞的生長(zhǎng)。Dvl和Wnt2是wnt信號(hào)通路的主要成員,位于整個(gè)信號(hào)轉(zhuǎn)導(dǎo)通路的上游,兩個(gè)蛋白在通路中的表達(dá)是wnt通路的在信號(hào)傳遞的關(guān)鍵環(huán)節(jié),兩個(gè)蛋白的表達(dá)異常,最終可導(dǎo)致β-catenin在胞漿內(nèi)水平增高累積入核,與轉(zhuǎn)錄因子相互作用,誘發(fā)靶基因的轉(zhuǎn)錄,參考以往的文獻(xiàn)Wnt/β-catenin通路的dvl和wnt2在食管癌、非細(xì)胞肺癌、腦膠質(zhì)瘤、乳腺癌、結(jié)腸癌中均有異常的表達(dá)。本研究通過(guò)免疫組化法檢測(cè)Dvl蛋白與Wnt2在喉鱗狀細(xì)胞癌及癌癥周邊正常組織中的表達(dá),探討兩個(gè)蛋白在年齡,發(fā)生部位,臨床分期、轉(zhuǎn)移情況、是否吸煙在癌癥及周邊的組織的表達(dá)水平,探討Dvl蛋白與Wnt2在喉癌的表達(dá)情況及相關(guān)性,分析探討Dvl與Wnt2在喉癌中的發(fā)病機(jī)制,為尋找新的治療途徑提供一個(gè)新思路。方法:1研究對(duì)象1.1石蠟標(biāo)本的收集選取河北醫(yī)科大學(xué)第四醫(yī)院耳鼻喉-頭頸外科2014年10月至2016年11月期間在河北醫(yī)科大學(xué)第四醫(yī)院住院的喉腫物手術(shù)患者,其中實(shí)驗(yàn)組為48例,經(jīng)病理確定為鱗狀細(xì)胞癌的患者,經(jīng)證實(shí)病歷資料采集證實(shí)此組患者選擇在術(shù)前均未行放、化療等治療,年齡43~71歲,平均58歲,對(duì)照組為24例喉癌患者的癌旁正常粘膜組織,距離癌原發(fā)部位0.5厘米。使用免疫組織化學(xué)(immunohistochemistry,IHC)S-P法對(duì)實(shí)驗(yàn)組和對(duì)照組中的Dvl及Wnt2的表達(dá)情況進(jìn)行檢測(cè)。1.2所有實(shí)驗(yàn)數(shù)據(jù)結(jié)果均使用SPSS21.0軟件進(jìn)行統(tǒng)計(jì)學(xué)分析,采用χ2檢驗(yàn),P0.05為有統(tǒng)計(jì)學(xué)意義。結(jié)果:1 Dvl的表達(dá)結(jié)果Dvl蛋白的蛋白陽(yáng)性表達(dá)均呈棕黃色或棕褐色,主要定位在細(xì)胞質(zhì)中,大多呈彌漫性表達(dá)。Dvl的表達(dá)在喉癌組織中的陽(yáng)性表達(dá)率(79.2%)明顯高于癌旁正常組織的陽(yáng)性表達(dá)率(33.3%),兩組經(jīng)檢驗(yàn)比較有統(tǒng)計(jì)學(xué)意義(P0.05)。1.1 Dvl在低分化、中高分化病理分型的陽(yáng)性表達(dá)率分別為89.4%,65.5%,說(shuō)明Dvl的在癌組織的表達(dá)隨著分化程度的降低而升高,經(jīng)統(tǒng)計(jì)學(xué)分析差異有統(tǒng)計(jì)學(xué)意義(P0.05)。1.2 Dvl蛋白的表達(dá)和臨床分期有相關(guān)性,臨床分期Ⅰ+Ⅱ的陽(yáng)性表達(dá)(57.1%)明顯低于Ⅲ+Ⅳ的表達(dá)(85.5%),經(jīng)統(tǒng)計(jì)學(xué)分析差異有統(tǒng)計(jì)學(xué)意義(P0.05)。1.3 Dvl蛋白表達(dá)在有淋巴結(jié)轉(zhuǎn)移的癌癥組織表達(dá)(84.6%),明顯高于無(wú)淋巴結(jié)轉(zhuǎn)移的表達(dá)(63.6%),經(jīng)統(tǒng)計(jì)學(xué)分析差異有統(tǒng)計(jì)學(xué)意義(P0.05)。1.4 Dvl蛋白在喉癌組的表達(dá)與患者的年齡、性別無(wú)明顯相關(guān)性(P0.05)。2 Wnt2表達(dá)結(jié)果2.1 Wnt2的陽(yáng)性物質(zhì)主要在細(xì)胞質(zhì),呈黃色或棕黃色顆粒。Wnt2在喉癌組織中的陽(yáng)性表達(dá)(75.0%)明顯高于癌旁組織的陽(yáng)性表達(dá)(45.8%),兩組經(jīng)檢驗(yàn)差異有統(tǒng)計(jì)學(xué)意義(P0.05)。2.2 Wnt2的表達(dá)在低分化及中高分化喉癌組織中的表達(dá)分別為84.20%,58.60%,患者分化程度越低,wnt2的陽(yáng)性表達(dá)越高,相反分化程度高的表達(dá)陽(yáng)性率偏低,經(jīng)統(tǒng)計(jì)學(xué)分析差異有統(tǒng)計(jì)學(xué)意義(P0.05)。2.3 Wnt2的表達(dá)與臨床分期有相關(guān)性,臨床分期越晚,wnt2表達(dá)就越強(qiáng),在Ⅲ、Ⅳ期的陽(yáng)性表達(dá)率(80.0%)明顯高于Ⅰ、Ⅱ期的陽(yáng)性表達(dá)率(60.7%),經(jīng)統(tǒng)計(jì)學(xué)分析差異有統(tǒng)計(jì)學(xué)意義(P0.05)。2.4 Wnt2在伴有淋巴轉(zhuǎn)移的喉癌組織中的表達(dá)(84.6%)明顯高于無(wú)淋巴轉(zhuǎn)移的癌組織表達(dá)(59.1%),經(jīng)統(tǒng)計(jì)學(xué)分析差異有統(tǒng)計(jì)學(xué)意義(P0.05)。3 Dvl與Wnt2表達(dá)之間的相關(guān)性Dvl與Wnt2在喉鱗狀細(xì)胞癌中的表達(dá)相關(guān)性分析,兩者的表達(dá)屬于正相關(guān)關(guān)系(r=0.537,P0.001)。結(jié)論:1喉鱗狀細(xì)胞癌組織中的Dvl和Wnt2的均有表達(dá),但喉癌組織中的陽(yáng)性表達(dá)率明顯高于癌旁正常黏膜組織,提示兩者可能參與喉癌的發(fā)生和發(fā)展,并激發(fā)癌組織的惡性程度和淋巴結(jié)轉(zhuǎn)移。2喉癌組織中的Dvl表達(dá)與臨床分期,分化程度和淋巴結(jié)轉(zhuǎn)移都存在高表達(dá),提示Dvl蛋白的高表達(dá)可能在喉癌的發(fā)展、浸潤(rùn)及轉(zhuǎn)移中起重要的作用。3 Wnt2在喉癌的臨床分期、分化程度和淋巴結(jié)轉(zhuǎn)移中都有高表達(dá),提示W(wǎng)nt2蛋白可能促進(jìn)喉癌的發(fā)展,并可能是喉鱗狀細(xì)胞癌的特征性的標(biāo)記物。4 Dvl蛋白與Wnt2蛋白在喉癌中的表達(dá)有正相關(guān)性,兩者可能通過(guò)某一個(gè)機(jī)制在喉癌的發(fā)生及發(fā)展中起促進(jìn)作用,為喉癌的靶向治療提供了一個(gè)新的依據(jù),但是是否能成為喉癌的新治療方法還需臨床進(jìn)一步驗(yàn)證。
[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.

【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】：2017
【分類號(hào)】：R739.65

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