食管腺癌組織中CAIX蛋白的表達(dá)及其臨床意義
發(fā)布時(shí)間：2018-11-19 18:00
【摘要】：背景與目的食管癌(Esophageal cancinoma,EC)是常見的消化道實(shí)體惡性腫瘤,在所有惡性腫瘤占2%,居全球第七位,是我國最常見的六大腫瘤之一。食管腺癌(esophageal adenocarcinoma,EAC)是食管癌常見的病理類型之一,在西方國家以食管腺癌為主,在我國食管腺癌的發(fā)病率僅次于食管鱗狀細(xì)胞癌(Esophageal squamous cell carcinoma,ESCC)。在中國原發(fā)食管腺癌的發(fā)病率占食管癌的5%-10%;食管腺癌患者的五年生存率約為10%,手術(shù)后的五年生存率較非手術(shù)的高,手術(shù)后約為15%-40%。全世界每年死于食管癌的人約30萬,但我國約占15萬。據(jù)預(yù)測(cè),癌癥的死亡率還在持續(xù)增長(zhǎng),到2030年估計(jì)將有1.1億人死于癌癥。目前,包括中國在內(nèi)的世界性范圍內(nèi),食管腺癌發(fā)生率呈逐年明顯升高的趨勢(shì)。雖有研究表明,早期食管癌患者行手術(shù)根治術(shù)可以達(dá)到滿意效果,但因?yàn)樵缙诎Y狀不明顯、特異性不高,而且大多數(shù)患者在發(fā)病早期進(jìn)食哽咽感、胸骨后疼痛等不在意,因此初診時(shí)多數(shù)患者就已經(jīng)進(jìn)入中晚期。對(duì)于食管腺癌的診療來說,探索尋求一種新的方法和思路非常重要。目前,食管癌的治療有多種手段,最主要方式是采用外科手術(shù)方法(病變組織切除并作消化道重建),依據(jù)實(shí)際情況配合放化療、生物免疫治療、中醫(yī)中藥等綜合治療。以上方法作為傳統(tǒng)的治療方式,但是對(duì)于不能行根治手術(shù)的晚期患者,特別是不能耐受手術(shù),生活質(zhì)量和生存期得不到明顯改善,不能耐受治療副作用出現(xiàn)病情加重甚至死亡。因此,對(duì)于食管癌來說,尋求探索研發(fā)一種新型的、有效的診療方法十分必要。隨著技術(shù)的進(jìn)步,DNA重組技術(shù)的逐步完善,腫瘤的免疫靶向治療技術(shù)也在快速發(fā)展,在未來有可能成為主要的診療手段。食管癌是常見消化系統(tǒng)惡性腫瘤之一,其發(fā)病是多階段、多因素、多基因共同作用的結(jié)果,研究其發(fā)病機(jī)制對(duì)食管癌的診斷及治療意義重大。本研究針對(duì)CA IX在食管腺癌中表達(dá)情況進(jìn)行研究,探討食管腺癌的發(fā)病機(jī)理,為靶向治療提供研究基礎(chǔ)。碳酸酐酶IX(carbonic anhydras IX,CA IX)為一個(gè)跨膜蛋白,已為腫瘤相關(guān)蛋白,主要在正常人上消化道及胰腺、膽囊、肝臟等相關(guān)器官中表達(dá),其他正常組織幾乎不表達(dá),而在許多實(shí)體瘤中高度表達(dá),并參與腫瘤細(xì)胞的增殖、轉(zhuǎn)移和侵襲相關(guān)。CA IX對(duì)放療及化療產(chǎn)生耐受,且促使惡化,加快癌細(xì)胞增殖與轉(zhuǎn)移。快速生長(zhǎng)的腫瘤細(xì)胞促使氧化磷酸化、無氧酵解等,使腫瘤微環(huán)境改變易缺血、缺氧。CA IX使腫瘤細(xì)胞內(nèi)堿外酸,這為腫瘤的生長(zhǎng)、轉(zhuǎn)移和侵襲創(chuàng)造了條件。CAⅨ蛋白在國內(nèi)對(duì)于腺癌的研究甚少,而且目前關(guān)于CA IX在食管腺癌組織中的表達(dá)情況國內(nèi)尚無報(bào)告。因此,研究CA IX在食管腺癌組織中的表達(dá),探討在食管癌發(fā)病中的作用,可為臨床診治及預(yù)后判斷提供新的理論依據(jù)。方法1.采用免疫組化SP的方法檢測(cè)45例食管腺癌組織、癌旁不典型增生及正常食管組織中CA IX蛋白的表達(dá)情況;應(yīng)用RT-PCR方法分析在食管腺癌組織、癌旁不典型增生及正常食管組織中表達(dá)分布情況,并分別分析CA IX的表達(dá)水平與臨床病理特征的關(guān)系。2.應(yīng)用SPSS 17.0進(jìn)行統(tǒng)計(jì)分析,正態(tài)分布的計(jì)量資料用均數(shù)±標(biāo)準(zhǔn)差(X±S)表示,兩組間比較采用t檢驗(yàn),重復(fù)測(cè)量資料采用重復(fù)測(cè)量數(shù)據(jù)方差分析;計(jì)數(shù)資料采用頻數(shù)和比分?jǐn)?shù)(率)表示,率的比較采用χ2檢驗(yàn),表達(dá)的關(guān)聯(lián)性分析采用Pearson列聯(lián)系數(shù);兩組間比較采用χ2檢驗(yàn),配對(duì)計(jì)數(shù)資料采用配對(duì)χ2檢驗(yàn);P0.05差異有統(tǒng)計(jì)學(xué)意義。結(jié)果CAⅨ蛋白在食管腺癌組織、癌旁不典型增生和正常食管組織中的陽性表達(dá)率依次為66.7%(30/45),24.4%(11/45),4.4%(2/45),三者兩兩比較具有統(tǒng)計(jì)學(xué)差異(χ2=41.845,P=0.001)。食管腺癌組織中CAⅨ蛋白的表達(dá)與腫瘤浸潤(rùn)深度、淋巴結(jié)轉(zhuǎn)移、分化程度及臨床分期有關(guān)(P=0.001),與性別年齡無關(guān)(P=0.664)。RT-PCR結(jié)果顯示CAⅨ基因在食管不同組織中均有表達(dá),分別為0.217±0.017,0.436±0.03,0.544±0.043,差異有統(tǒng)計(jì)學(xué)意義(χ2=60.614,P=0.001)。結(jié)論CAⅨ蛋白可能參與食管腺癌的發(fā)生發(fā)展,對(duì)于CAⅨ蛋白進(jìn)行檢測(cè)有助于食管腺癌的診斷治療。
[Abstract]:Background and target esophageal cancer (EC) is a common malignant tumor of the digestive tract, accounting for 2% of all the malignant tumors and the seventh in the world. It is one of the most common tumors in our country. EAC, one of the most common types of esophageal adenocarcinoma, is the most common type of esophageal adenocarcinoma in the western countries. The incidence of esophageal adenocarcinoma in our country is only after the esophageal squamous cell carcinoma (ESCC). The incidence of primary esophageal adenocarcinoma in China accounts for 5-10% of the esophageal cancer, the five-year survival rate of the patients with esophageal adenocarcinoma is about 10%, the five-year survival rate after operation is higher than that of the non-operative, and the operation is about 15% -40%. About 300,000 people die from the world every year, but about 150,000 in our country. The death rate of cancer is also forecast to continue to grow, and by 2030 it is estimated that there will be 1. 100 million people to die in cancer. At present, the incidence of esophageal adenocarcinoma is in the worldwide range, including China, and the incidence of esophageal adenocarcinoma is increasing year by year. The results show that the radical operation of the patients with early esophageal cancer can achieve the satisfactory effect, but because the early symptoms are not clear, the specificity is not high, and most of the patients are not concerned about the early stage of the onset of food, the sense of the pharynx, the back pain of the sternum, and the like, Therefore, most of the patients in the first visit have entered the middle and late stage. It is very important for the diagnosis and treatment of esophageal adenocarcinoma to find a new method and thought. At present, the treatment of the esophagus cancer has various means, the most important way is to adopt the surgical method (the pathological tissue is cut off and the digestive tract is reconstructed), and according to the actual situation, cooperate with the radiotherapy and chemotherapy, the biological immunotherapy, the traditional Chinese medicine and other comprehensive treatment. The above method is used as a traditional treatment method, but for the advanced patients who cannot perform radical operation, in particular, the operation can not be tolerated, the quality of life and the survival time are not obviously improved, and the occurrence of the side effects of the treatment cannot be tolerated and even the death can not be tolerated. Therefore, it is necessary to search for a new and effective method of diagnosis and development for esophageal cancer. With the progress of the technology and the gradual improvement of DNA recombination technology, the immune-targeted therapy technology of the tumor is also rapidly developing, and it is possible to become the main diagnosis and treatment means in the future. Esophageal cancer is one of the most common malignant tumors of the digestive system. The pathogenesis of esophageal cancer is the result of multi-stage, multi-factor and multi-gene co-operation, and its pathogenesis is of great significance to the diagnosis and treatment of esophageal cancer. In this study, the expression of CA IX in esophageal adenocarcinoma was studied, and the pathogenesis of esophageal adenocarcinoma was discussed. Carbonic anhydra IX (CA IX) is a transmembrane protein, which is a tumor-related protein, and is mainly expressed in related organs such as the upper gastrointestinal tract of the normal person and the pancreas, the gallbladder, the liver and the like, and the other normal tissues are hardly expressed, and are highly expressed in many solid tumors, and involved in the proliferation, metastasis and invasion of the tumor cells. CA IX is resistant to radiotherapy and chemotherapy, and promotes the deterioration of cancer cells and accelerates the proliferation and metastasis of cancer cells. the rapidly growing tumor cells promote oxidative phosphorylation, anaerobic glycolysis, and the like, so that the micro-environment of the tumor can be changed to be ischemia and hypoxia. The CA IX makes the extracellular acid in the tumor cell, which creates conditions for the growth, metastasis and invasion of the tumor. The CA-IX protein has little research on adenocarcinoma in China, and there is no report on the expression of CA IX in the tissue of esophageal adenocarcinoma. Therefore, the study of the expression of CA IX in the tissue of esophageal adenocarcinoma and the role of CA IX in the pathogenesis of esophageal cancer can provide a new theoretical basis for clinical diagnosis and treatment and prognosis. Method 1. The expression of CA IX in 45 cases of esophageal adenocarcinoma, atypical hyperplasia and normal esophageal tissues was detected by the method of SP. The distribution of the expression of CA IX in the tissues of esophageal adenocarcinoma, atypical hyperplasia and normal esophageal tissues was analyzed by RT-PCR. The relationship between the expression level of CA IX and the clinical pathological characteristics was analyzed. The statistical analysis was carried out with SPSS 10.0. The mean square standard deviation (X-S) of the measurement data of normal distribution indicated that t-test was adopted between the two groups, and the data of repeated measurement was used to measure the variance of data. The frequency and the specific fraction (rate) were used to count the data. The results showed that the correlation between the two groups was the Pearson column contact number. The comparison between the two groups was the second test, and the paired count data were tested by the paired-2 test; the difference between the two groups was statistically significant. Results The positive expression rates of CA-2 in esophageal adenocarcinoma, atypical hyperplasia and normal esophageal tissues were 60.7% (30/ 45), 24. 4% (11/ 45) and 4. 4% (2/ 45), respectively. The expression of CA-2 in esophageal adenocarcinoma was related to the depth of tumor invasion, lymph node metastasis, degree of differentiation and clinical stage (P = 0.001). The results of RT-PCR showed that the CA-2 gene was expressed in different tissues of the esophagus, 0.217-0.017, 0.436-0.03, 0.544-0.043, respectively. The difference was statistically significant (Sup2 = 60.614, P = 0.001). Conclusion CA-2 protein may be involved in the development of esophageal adenocarcinoma, and it can be used for the diagnosis and treatment of esophageal adenocarcinoma.
【學(xué)位授予單位】：鄭州大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2016
【分類號(hào)】：R735.1
本文編號(hào)：2343011
[Abstract]:Background and target esophageal cancer (EC) is a common malignant tumor of the digestive tract, accounting for 2% of all the malignant tumors and the seventh in the world. It is one of the most common tumors in our country. EAC, one of the most common types of esophageal adenocarcinoma, is the most common type of esophageal adenocarcinoma in the western countries. The incidence of esophageal adenocarcinoma in our country is only after the esophageal squamous cell carcinoma (ESCC). The incidence of primary esophageal adenocarcinoma in China accounts for 5-10% of the esophageal cancer, the five-year survival rate of the patients with esophageal adenocarcinoma is about 10%, the five-year survival rate after operation is higher than that of the non-operative, and the operation is about 15% -40%. About 300,000 people die from the world every year, but about 150,000 in our country. The death rate of cancer is also forecast to continue to grow, and by 2030 it is estimated that there will be 1. 100 million people to die in cancer. At present, the incidence of esophageal adenocarcinoma is in the worldwide range, including China, and the incidence of esophageal adenocarcinoma is increasing year by year. The results show that the radical operation of the patients with early esophageal cancer can achieve the satisfactory effect, but because the early symptoms are not clear, the specificity is not high, and most of the patients are not concerned about the early stage of the onset of food, the sense of the pharynx, the back pain of the sternum, and the like, Therefore, most of the patients in the first visit have entered the middle and late stage. It is very important for the diagnosis and treatment of esophageal adenocarcinoma to find a new method and thought. At present, the treatment of the esophagus cancer has various means, the most important way is to adopt the surgical method (the pathological tissue is cut off and the digestive tract is reconstructed), and according to the actual situation, cooperate with the radiotherapy and chemotherapy, the biological immunotherapy, the traditional Chinese medicine and other comprehensive treatment. The above method is used as a traditional treatment method, but for the advanced patients who cannot perform radical operation, in particular, the operation can not be tolerated, the quality of life and the survival time are not obviously improved, and the occurrence of the side effects of the treatment cannot be tolerated and even the death can not be tolerated. Therefore, it is necessary to search for a new and effective method of diagnosis and development for esophageal cancer. With the progress of the technology and the gradual improvement of DNA recombination technology, the immune-targeted therapy technology of the tumor is also rapidly developing, and it is possible to become the main diagnosis and treatment means in the future. Esophageal cancer is one of the most common malignant tumors of the digestive system. The pathogenesis of esophageal cancer is the result of multi-stage, multi-factor and multi-gene co-operation, and its pathogenesis is of great significance to the diagnosis and treatment of esophageal cancer. In this study, the expression of CA IX in esophageal adenocarcinoma was studied, and the pathogenesis of esophageal adenocarcinoma was discussed. Carbonic anhydra IX (CA IX) is a transmembrane protein, which is a tumor-related protein, and is mainly expressed in related organs such as the upper gastrointestinal tract of the normal person and the pancreas, the gallbladder, the liver and the like, and the other normal tissues are hardly expressed, and are highly expressed in many solid tumors, and involved in the proliferation, metastasis and invasion of the tumor cells. CA IX is resistant to radiotherapy and chemotherapy, and promotes the deterioration of cancer cells and accelerates the proliferation and metastasis of cancer cells. the rapidly growing tumor cells promote oxidative phosphorylation, anaerobic glycolysis, and the like, so that the micro-environment of the tumor can be changed to be ischemia and hypoxia. The CA IX makes the extracellular acid in the tumor cell, which creates conditions for the growth, metastasis and invasion of the tumor. The CA-IX protein has little research on adenocarcinoma in China, and there is no report on the expression of CA IX in the tissue of esophageal adenocarcinoma. Therefore, the study of the expression of CA IX in the tissue of esophageal adenocarcinoma and the role of CA IX in the pathogenesis of esophageal cancer can provide a new theoretical basis for clinical diagnosis and treatment and prognosis. Method 1. The expression of CA IX in 45 cases of esophageal adenocarcinoma, atypical hyperplasia and normal esophageal tissues was detected by the method of SP. The distribution of the expression of CA IX in the tissues of esophageal adenocarcinoma, atypical hyperplasia and normal esophageal tissues was analyzed by RT-PCR. The relationship between the expression level of CA IX and the clinical pathological characteristics was analyzed. The statistical analysis was carried out with SPSS 10.0. The mean square standard deviation (X-S) of the measurement data of normal distribution indicated that t-test was adopted between the two groups, and the data of repeated measurement was used to measure the variance of data. The frequency and the specific fraction (rate) were used to count the data. The results showed that the correlation between the two groups was the Pearson column contact number. The comparison between the two groups was the second test, and the paired count data were tested by the paired-2 test; the difference between the two groups was statistically significant. Results The positive expression rates of CA-2 in esophageal adenocarcinoma, atypical hyperplasia and normal esophageal tissues were 60.7% (30/ 45), 24. 4% (11/ 45) and 4. 4% (2/ 45), respectively. The expression of CA-2 in esophageal adenocarcinoma was related to the depth of tumor invasion, lymph node metastasis, degree of differentiation and clinical stage (P = 0.001). The results of RT-PCR showed that the CA-2 gene was expressed in different tissues of the esophagus, 0.217-0.017, 0.436-0.03, 0.544-0.043, respectively. The difference was statistically significant (Sup2 = 60.614, P = 0.001). Conclusion CA-2 protein may be involved in the development of esophageal adenocarcinoma, and it can be used for the diagnosis and treatment of esophageal adenocarcinoma.
【學(xué)位授予單位】：鄭州大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2016
【分類號(hào)】：R735.1
【相似文獻(xiàn)】
相關(guān)期刊論文 前10條
1 李易,韓盛璽,沈通良;食管腺癌41例分析[J];四川醫(yī)學(xué);2002年06期
2 章宏,厲有名,王偉;食管腺癌臨床流行病學(xué)研究[J];中華消化雜志;2003年11期
3 Lepage C.;Bouvier A.-M.;Manfredi S. ;J. Faivre;王曉君;;特定人群食管腺癌的發(fā)病趨勢(shì)與治療[J];世界核心醫(yī)學(xué)期刊文摘(胃腸病學(xué)分冊(cè));2006年Z1期
4 王純巍;反流增加食管腺癌的危險(xiǎn)[J];英國醫(yī)學(xué)雜志(中文版);1999年04期
5 黎榮光,鄒浩元,黃國棟,張漢雄;食管腺癌放射治療20例報(bào)告[J];腫瘤研究與臨床;2001年04期
6 文載律,羅偉,李文才,梁麗麗,季磊;食管腺癌77例臨床病理分析[J];診斷病理學(xué)雜志;2002年03期
7 莫宏波,劉譽(yù),陳萬群;食管腺癌生物標(biāo)記物的研究進(jìn)展[J];腫瘤防治研究;2005年08期
8 孫永剛;周鋼;王偉強(qiáng);楊仕明;汪榮泉;房殿春;;食管腺癌組織中核干細(xì)胞因子表達(dá)的研究[J];胃腸病學(xué)和肝病學(xué)雜志;2009年06期
9 程鵬;李建生;;不同反流物對(duì)十二指腸胃混合食管反流大鼠食管腺癌發(fā)生的影響[J];鄭州大學(xué)學(xué)報(bào)(醫(yī)學(xué)版);2011年03期
10 盧嘉臻;王雯;張志堅(jiān);李達(dá)周;王蓉;;食管腺癌與賁門腺癌的臨床病理特點(diǎn)分析[J];福州總醫(yī)院學(xué)報(bào);2011年02期
相關(guān)會(huì)議論文 前1條
1 張遜;David I Watson;Justin R Bessell;;食管腺癌侵及深度及淋巴結(jié)轉(zhuǎn)移與腫瘤預(yù)后的關(guān)系[A];中華醫(yī)學(xué)會(huì)第六次全國胸心血管外科學(xué)術(shù)會(huì)議論文集（胸外科分冊(cè)）[C];2006年
相關(guān)重要報(bào)紙文章 前1條
1 武漢同濟(jì)醫(yī)院腫瘤中心主任 于世英;胖人更易得癌癥[N];健康報(bào);2008年
相關(guān)博士學(xué)位論文 前1條
1 張濤;選擇性環(huán)氧合酶-2抑制劑塞來昔布用于食管腺癌化學(xué)預(yù)防的實(shí)驗(yàn)研究[D];第四軍醫(yī)大學(xué);2004年
相關(guān)碩士學(xué)位論文 前10條
1 李娜;食管腺癌臨床病理特征及治療模式探討[D];河北醫(yī)科大學(xué);2015年
2 邵順子;重慶地區(qū)食管腺癌和賁門腺癌胃鏡檢出率變化-35年回顧性分析[D];第三軍醫(yī)大學(xué);2015年
3 王恒;食管腺癌組織中CAIX蛋白的表達(dá)及其臨床意義[D];鄭州大學(xué);2016年
4 何旭;食管腺癌臨床預(yù)后相關(guān)因素分析[D];河北醫(yī)科大學(xué);2013年
5 穆華;酪酪肽和維生素E琥珀酸酯對(duì)人食管腺癌SEG-1細(xì)胞增殖與凋亡的影響[D];河北醫(yī)科大學(xué);2008年
6 魯玉娟;胃泌素及其受體在人食管腺癌細(xì)胞增殖中的作用[D];河北醫(yī)科大學(xué);2008年
7 鄧友君;抑癌基因NDRG2在食管腺癌中的表達(dá)及臨床意義[D];遵義醫(yī)學(xué)院;2014年
8 張濤;反流誘發(fā)Barrett’s食管、食管腺癌及其發(fā)展過程中誘導(dǎo)型一氧化氮合酶表達(dá)及意義的實(shí)驗(yàn)研究[D];第四軍醫(yī)大學(xué);2001年
9 王哲;食管腺癌患者血液中外排小體微小RNA的研究[D];河北醫(yī)科大學(xué);2014年
10 蔣承霖;E-cadherin、β-catenin在Barrett食管、食管腺癌中的表達(dá)及意義[D];福建醫(yī)科大學(xué);2010年
，本文編號(hào)：2343011
本文鏈接：http://sikaile.net/yixuelunwen/zlx/2343011.html
最近更新
教材專著
