本文選題：結(jié)腸惡性腫瘤 + Six1��； 參考：《承德醫(yī)學(xué)院》2017年碩士論文

【摘要】：縱觀消化道環(huán)球發(fā)病率最高的幾種惡性疾病中結(jié)腸癌的占有比率愈來(lái)愈高。結(jié)腸癌在我國(guó)的發(fā)病率及死亡率亦較前大幅增長(zhǎng)。以往眾多研究結(jié)論顯示,結(jié)腸癌患者治愈率降低、死亡率升高的關(guān)鍵因素是發(fā)生轉(zhuǎn)移,而結(jié)腸癌的發(fā)生發(fā)展是包含多個(gè)階段涉及很多因素的綜合復(fù)雜病理過(guò)程,防治結(jié)腸癌的轉(zhuǎn)移成為醫(yī)務(wù)工作者一直以來(lái)較難攻克的難題。然而,隨著上皮間質(zhì)細(xì)胞轉(zhuǎn)化(EMT)的發(fā)現(xiàn)及其在惡性腫瘤中的深入研究,提示包括結(jié)腸癌在內(nèi)許多腫瘤細(xì)胞浸潤(rùn)、早期轉(zhuǎn)移過(guò)程中發(fā)生了EMT,因此,通過(guò)探索結(jié)腸癌EMT相關(guān)分子機(jī)制,為提高結(jié)腸癌患者生存率及改善預(yù)后提供較為可能的有效途徑。同源盒基因1(Six1)可與DNA特定部位結(jié)合,特異性調(diào)節(jié)下游基因的表達(dá),為同源盒基因家族成員,在細(xì)胞增殖、分化、黏著、轉(zhuǎn)移等重要過(guò)程作用關(guān)鍵。EMT是30多年前已經(jīng)被提出的一個(gè)分子事件,它是指上皮細(xì)胞在某些病理或生理?xiàng)l件下轉(zhuǎn)變成具有移動(dòng)能力的間質(zhì)細(xì)胞的過(guò)程。大量的研究已經(jīng)表明,其與大部分惡性腫瘤的原發(fā)性浸潤(rùn)和繼發(fā)性轉(zhuǎn)移密不可分。隨著研究的不斷深入,越來(lái)越多EMT相關(guān)的關(guān)鍵調(diào)節(jié)因子和通路被不斷發(fā)現(xiàn)和完善。Six1蛋白是近年來(lái)研究EMT相關(guān)分子的熱點(diǎn)轉(zhuǎn)錄調(diào)節(jié)因子之一,目前已有研究提示,細(xì)胞周期的調(diào)控、胚胎生長(zhǎng)和器官成熟、癌細(xì)胞的激活及轉(zhuǎn)移的推動(dòng)等過(guò)程都與Six1有關(guān)。其在腫瘤細(xì)胞中高表達(dá),通過(guò)誘導(dǎo)細(xì)胞增生、抑制凋亡,甚至為惡性細(xì)胞創(chuàng)造EMT發(fā)生條件而促進(jìn)轉(zhuǎn)移等過(guò)程,參與腫瘤發(fā)生發(fā)展。叉頭框蛋白C2(Forkhead box protein C2,FOXC2),也被稱(chēng)為間充質(zhì)叉頭蛋白1(Mesenchyme fork head protein 1,MFHl),與叉頭框家族其他成員一樣具有特定DNA結(jié)合域,參與DNA轉(zhuǎn)錄過(guò)程。研究發(fā)現(xiàn),FOXC2是EMT的重要調(diào)節(jié)者之一,其他某些EMT相關(guān)轉(zhuǎn)錄因子受FOXC2誘導(dǎo)表達(dá),同時(shí)FOXC2也能正向提高自身在上皮細(xì)胞中的表達(dá),而且還可上調(diào)基質(zhì)金屬蛋白酶2(MMP-2)和基質(zhì)金屬蛋白酶9(MMP-9)的水平,促進(jìn)間質(zhì)分化及細(xì)胞的移動(dòng),進(jìn)而為協(xié)助腫瘤細(xì)胞在臨近組織中的浸潤(rùn)和遠(yuǎn)處臟器的轉(zhuǎn)移提供基礎(chǔ)。E-鈣黏蛋白(E-cad)遍及各種上皮細(xì)胞表面分布,起到促進(jìn)細(xì)胞間相互銜接粘著功能,是保持細(xì)胞極性、維持細(xì)胞形態(tài)的結(jié)構(gòu)分子,同時(shí)也是介導(dǎo)上皮細(xì)胞之間及其與基質(zhì)間通信的媒介。E-cad缺失表達(dá)或功能缺損后上皮細(xì)胞可經(jīng)歷改變極性、降低黏附力等過(guò)程,最終呈現(xiàn)非上皮特征。經(jīng)研究發(fā)現(xiàn),在上皮細(xì)胞發(fā)生EMT過(guò)程中,E-cad表達(dá)下調(diào)是普遍現(xiàn)象,它的表達(dá)缺失在細(xì)胞惡性表型的轉(zhuǎn)變中具有因果關(guān)系,所以E-cad的表達(dá)下調(diào)是EMT的最顯著性的特征之一。目的:通過(guò)檢測(cè)Six1、FOXC2及E-cad在結(jié)腸癌及癌旁正常結(jié)腸組織中的表達(dá)水平,剖析結(jié)腸癌中Six1、FOXC2及E-cad的表達(dá)水平與臨床病理特征及在腫瘤增殖發(fā)展過(guò)程中彼此之間的相關(guān)性。Six1、FOXC2為腫瘤發(fā)生發(fā)展治療新靶點(diǎn)提供新的理論基礎(chǔ)以及聯(lián)合檢測(cè)三者為判斷臨床預(yù)后提供更多的依據(jù)。方法:收集病理明確診斷為結(jié)腸腺癌的蠟塊固定組織70例和癌旁正常結(jié)腸蠟塊固定組織35例,術(shù)前患者均無(wú)實(shí)行放療、化療等任何新輔助治療。用免疫組織化學(xué)法檢測(cè)結(jié)腸癌組織中Six1、FOXC2及E-cad表達(dá)水平,分析性別、年齡、腫瘤大小、浸潤(rùn)深度及淋巴結(jié)轉(zhuǎn)移與它們是否存在相關(guān)性。數(shù)據(jù)分析使用SPSS 19.0,χ2檢驗(yàn)統(tǒng)計(jì)計(jì)數(shù)資料,Spearman秩相關(guān)分析判斷指標(biāo)間相關(guān)性,檢驗(yàn)標(biāo)準(zhǔn)為α=0.05,以P0.05為差異有統(tǒng)計(jì)學(xué)意義。結(jié)果:免疫組織化學(xué)結(jié)果1.Six1、FOXC2及E-cad在結(jié)腸癌組織和癌旁正常結(jié)腸組織中都有不同程度表達(dá)。Six1和FOXC2主要于細(xì)胞質(zhì)染色陽(yáng)性,在癌組織中的陽(yáng)性表達(dá)率分別為82.9%(58/70)和74.3%(52/70),均顯著高于癌旁正常組織中的陽(yáng)性表達(dá)率20.0%(7/35)和22.9%(8/35),差異均具有統(tǒng)計(jì)學(xué)意義(χ2=39.092,P=0.000;χ2=25.200,P=0.000)。E-cad主要于細(xì)胞膜染色陽(yáng)性,在結(jié)腸癌組織表達(dá)陽(yáng)性率為21.4%(15/70),與正常結(jié)腸組織中的表達(dá)陽(yáng)性率80.0%(28/35)比顯著降低,差異有統(tǒng)計(jì)學(xué)意義(χ2=33.103,P=0.000)。2.Six1、FOXC2及E-cad于結(jié)腸癌中的表達(dá)水平與性別、年齡、腫瘤大小、分化程度無(wú)關(guān)聯(lián),且相關(guān)性無(wú)統(tǒng)計(jì)學(xué)差異(P0.05),而與TNM分期、浸潤(rùn)深度及淋巴結(jié)轉(zhuǎn)移具有相關(guān)性,且具有統(tǒng)計(jì)學(xué)意義(P0.05)。3.在結(jié)腸癌中Six1與FOXC2的陽(yáng)性表達(dá)呈正相關(guān)(r=0.426,P0.01);E-cad的陽(yáng)性表達(dá)分別與Six1、FOXC2呈負(fù)相關(guān)(r=-0.480,P0.05;r=-0.728,P0.05),差異均具有統(tǒng)計(jì)學(xué)意義(P0.05)。結(jié)論:Six1、FOXC2在結(jié)腸癌組織中的陽(yáng)性率均明顯高于癌旁正常結(jié)腸組織,而E-cad在癌組織的陽(yáng)性率顯著降低,且三者在惡性組織中的表達(dá)均與腫瘤浸潤(rùn)深度、淋巴結(jié)轉(zhuǎn)移、TNM分期有關(guān)。侵襲管壁越深,有淋巴結(jié)轉(zhuǎn)移,TNM分期越晚,則Six1、FOXC2陽(yáng)性率越高,E-cad陽(yáng)性率越低,提示三者與結(jié)腸癌的惡性行為及預(yù)后判斷可能存在相關(guān)性,可較為敏感的提示癌細(xì)胞發(fā)生浸潤(rùn)轉(zhuǎn)移。Six1和FOXC2的陽(yáng)性表達(dá)呈正相關(guān),且二者均與E-cad呈負(fù)相關(guān)。而EMT會(huì)導(dǎo)致腫瘤浸潤(rùn)轉(zhuǎn)移,故聯(lián)合檢測(cè)三者的表達(dá)水平可能會(huì)在結(jié)腸癌EMT治療新靶點(diǎn)方面提供理論依據(jù),及進(jìn)一步探討其判斷結(jié)腸癌患者的臨床預(yù)后提供一定的研究基礎(chǔ)。
[Abstract]:The incidence of colon cancer in several malignant diseases with the highest incidence of global digestive tract is higher and higher. The incidence and mortality of colon cancer in China have also increased significantly. The complex pathological process involving many factors is involved in many factors, and the prevention and treatment of colon cancer has been a difficult problem for medical workers. However, with the discovery of epithelial mesenchymal cell transformation (EMT) and its deep study in malignant tumor, it suggests that many tumor cells including colon cancer, including the infiltration of cancer cells, and early metastasis. EMT has occurred in the process. Therefore, by exploring the EMT related molecular mechanism of colon cancer, it provides a more effective way to improve the survival rate and improve the prognosis of colon cancer patients. Homologous box gene 1 (Six1) can be combined with specific sites of DNA, specifically regulate the expression of downstream genes, for the family members of the homologous gene family, cell proliferation, differentiation, and adhesion. The key.EMT is a molecular event that has been proposed more than 30 years ago. It refers to the process of epithelial cells in some pathological or physiological conditions into a cell with a mobile capacity. A large number of studies have shown that the primary invasion and secondary metastasis of most malignant tumors are incompatible. In recent years, more and more key regulatory factors and pathways related to EMT have been discovered and perfected by more and more.Six1 proteins, which are one of the hot transcriptional regulators for the study of EMT related molecules in recent years. There have been some research on the regulation of cell cycle, embryo growth and organ maturation, the promotion of cancer cell activation and metastasis. The process is related to Six1, which is highly expressed in tumor cells, and is involved in the development of tumor by inducing cell proliferation, inhibiting apoptosis and even creating EMT conditions for malignant cells, and involved in the development of tumor. Forkhead box protein C2 (FOXC2), also known as mesenchymal fork head protein 1 (Mesenchyme fork head protein 1,) MFHl), as with other members of the forked frame family, has a specific DNA binding domain and participates in the DNA transcriptional process. It is found that FOXC2 is one of the important regulators of EMT. Some of the other EMT related transcription factors are induced by FOXC2, and FOXC2 can positively increase its expression in the epithelial cells, and also up regulation of matrix metalloproteinase 2 (MMP). -2) and matrix metalloproteinase 9 (MMP-9) levels, promoting interstitial differentiation and cell migration, and providing the basis for assisting tumor cells to infiltrate in adjacent tissues and metastasis of distant organs to provide the basis for the distribution of.E- calcium mucin (E-cad) throughout the surface of epithelial cells, promoting intercellular adhesion and adhesion, and maintaining cell polarity. The structural molecules that maintain cell morphology are also a medium for mediating and communicating between the epithelial cells and the matrix between the medium.E-cad and the loss of function after the deletion of the epithelial cells. The epithelial cells can undergo the process of changing polarity, reducing adhesion and other processes, and eventually showing non epithelial characteristics. The study found that the down regulation of E-cad expression in the EMT process of epithelial cells is common. The expression of E-cad is one of the most significant characteristics of EMT. Objective: to analyze the expression level of Six1, FOXC2 and E-cad in colon and adjacent normal colonic tissues, and to analyze the expression level and clinical level of Six1, FOXC2 and E-cad in colon cancer. The pathological features and the correlation between each other in the process of tumor proliferation and development.Six1, FOXC2 provides a new theoretical basis for the new target of tumor development and development, and the joint detection three provides more basis for judging the clinical prognosis. Methods: 70 cases of paraffin fixed tissue and normal paracancerous junctions of colon adenocarcinoma were diagnosed by collecting pathology. 35 cases of intestinal wax block fixed tissue, no new adjuvant therapy, such as radiotherapy and chemotherapy, were used before the operation. The expression of Six1, FOXC2 and E-cad in colon cancer tissue was detected by immunohistochemistry. The correlation between sex, age, tumor size, depth of invasion and lymph node metastasis was correlated with them. Data analysis used SPSS 19, chi 2 test Statistical count data, Spearman rank correlation analysis was used to determine the correlation between the indexes, the test standard was alpha =0.05, and the difference between P0.05 and 1.Six1, FOXC2 and E-cad in colon cancer tissues and normal colon tissues were different to some extent,.Six1 and FOXC2 were mainly positive for cytoplasmic staining and in cancer. The positive expression rates in the tissues were 82.9% (58/70) and 74.3% (52/70), respectively, which were significantly higher than those in the normal tissues by 20% (7/35) and 22.9% (8/35). The difference was statistically significant (x 2=39.092, P=0.000; Chi 2=25.200, P=0.000).E-cad mainly in cell membrane staining, and the positive rate in colon cancer tissue was 21.4% (15/70). The positive rate of expression of 80% (28/35) in the normal colonic tissue was significantly lower than that in the colon (x 2=33.103, P=0.000).2.Six1. The expression level of FOXC2 and E-cad in colon cancer was not associated with sex, age, tumor size, and degree of differentiation, and the correlation was not statistically significant (P0.05), but with TNM staging, infiltration depth and lymph node transfer. The positive expression of Six1 and FOXC2 in colon cancer was positively correlated (r=0.426, P0.01) in colon cancer (r=0.426, P0.01), and the positive expression of E-cad was negatively correlated with Six1 and FOXC2 respectively (r=-0.480, P0.05; r=-0.728, Six1). Conclusion: the positive rate of E-cad in colon cancer tissues is all The positive rate of E-cad in the normal colon was significantly higher than that in the cancer tissue, and the expression of the three in the malignant tissue was significantly lower, and the expression of the three in the malignant tissue was related to the depth of tumor infiltration, lymph node metastasis and TNM staging. The deeper the invasion tube wall, the metastasis of the lymph nodes, the later the TNM staging, the higher the positive rate of FOXC2, the lower the positive rate of E-cad, suggesting the three and the knot. There may be a correlation between the malignant behavior and prognosis of colorectal cancer. It is more sensitive to suggest that the positive expression of.Six1 and FOXC2 is positively correlated with the invasion and metastasis of cancer cells, and all of the two are negatively correlated with E-cad. And EMT may lead to tumor invasion and metastasis, so the expression level of the combined detection of the three may be in the new target of colon cancer EMT treatment. It provides a theoretical basis for further study of its clinical prognosis in colon cancer patients.
【學(xué)位授予單位】：承德醫(yī)學(xué)院
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類(lèi)號(hào)】：R735.35

【參考文獻(xiàn)】

相關(guān)期刊論文 前10條

1 宋玉蘭;孫平;郭妹;;MicroRNA在結(jié)腸癌EMT轉(zhuǎn)化中的作用與機(jī)制研究[J];江西醫(yī)藥;2016年06期

2 諸葛春鳳;劉詩(shī)權(quán);;上皮-間質(zhì)轉(zhuǎn)化在結(jié)直腸癌中的研究進(jìn)展[J];胃腸病學(xué);2016年05期

3 何俊君;劉龍飛;周賢;;結(jié)直腸癌中上皮間質(zhì)化相關(guān)轉(zhuǎn)錄調(diào)控和信號(hào)通路研究進(jìn)展[J];山東醫(yī)藥;2016年18期

4 蔡娟娟;崔艷梅;丁彥青;廖雯婷;;FOXC2對(duì)結(jié)直腸癌細(xì)胞上皮-間質(zhì)轉(zhuǎn)化及侵襲能力的影響[J];重慶醫(yī)學(xué);2016年11期

5 諸葛春鳳;劉詩(shī)權(quán);譚林;覃蒙斌;梁夢(mèng)紫;黃杰安;;SphK1和FAK對(duì)人結(jié)腸癌HCT116細(xì)胞上皮間質(zhì)轉(zhuǎn)化的影響[J];中國(guó)病理生理雜志;2016年03期

6 洪甜;李玲;李文超;郭靖;梁迎春;紀(jì)貝貝;梅國(guó)徽;徐小潔;葉棋濃;;人Six1基因缺失突變體對(duì)上皮鈣黏素(E-cadherin)啟動(dòng)子活性的影響[J];細(xì)胞與分子免疫學(xué)雜志;2016年02期

7 陳文浩;楊明;張艷橋;;上皮—間質(zhì)轉(zhuǎn)化在惡性腫瘤中發(fā)生機(jī)制的研究進(jìn)展[J];中國(guó)腫瘤;2016年01期

8 曹曉瑋;閻錫新;劉姣姣;楊濤;;HOXC6通過(guò)激活轉(zhuǎn)化生長(zhǎng)因子β信號(hào)通路增強(qiáng)腫瘤細(xì)胞活性[J];河北醫(yī)科大學(xué)學(xué)報(bào);2015年12期

9 陳穎;姜昊聲;馬俐君;柳思琪;金珍婧;徐慶;;RhoGDI2與EMT相關(guān)蛋白在結(jié)直腸癌組織中表達(dá)的臨床意義及相關(guān)性[J];中國(guó)實(shí)驗(yàn)診斷學(xué);2015年09期

10 屈晶晶;李敏;安健;胡成平;;上皮-間質(zhì)轉(zhuǎn)化與腫瘤轉(zhuǎn)移及干細(xì)胞的研究進(jìn)展[J];國(guó)際呼吸雜志;2015年12期

，

本文編號(hào)：1952113