發(fā)布時間：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%,手術后的五年生存率較非手術的高,手術后約為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)預測,癌癥的死亡率還在持續(xù)增長,到2030年估計將有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。雖有研究表明,早期食管癌患者行手術根治術可以達到滿意效果,但因為早期癥狀不明顯、特異性不高,而且大多數(shù)患者在發(fā)病早期進食哽咽感、胸骨后疼痛等不在意,因此初診時多數(shù)患者就已經(jīng)進入中晚期。對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方法(病變組織切除并作消化道重建),依據(jù)實際情況配合放化療、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,但是對于不能行根治手術的晚期患者,特別是不能耐受手術,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。隨著技術的進步,DNA重組技術的逐步完善,腫瘤的免疫靶向治療技術也在快速發(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果,研究其發(fā)病機制對食管癌的診斷及治療意義重大。本研究針對CA IX在食管腺癌中表達情況進行研究,探討食管腺癌的發(fā)病機理,為靶向治療提供研究基礎。碳酸酐酶IX(carbonic anhydras IX,CA IX)為一個跨膜蛋白,已為腫瘤相關蛋白,主要在正常人上消化道及胰腺、膽囊、肝臟等相關器官中表達,其他正常組織幾乎不表達,而在許多實體瘤中高度表達,并參與腫瘤細胞的增殖、轉(zhuǎn)移和侵襲相關。CA IX對放療及化療產(chǎn)生耐受,且促使惡化,加快癌細胞增殖與轉(zhuǎn)移�？焖偕L的腫瘤細胞促使氧化磷酸化、無氧酵解等,使腫瘤微環(huán)境改變易缺血、缺氧。CA IX使腫瘤細胞內(nèi)堿外酸,這為腫瘤的生長、轉(zhuǎn)移和侵襲創(chuàng)造了條件。CAⅨ蛋白在國內(nèi)對于腺癌的研究甚少,而且目前關于CA IX在食管腺癌組織中的表達情況國內(nèi)尚無報告。因此,研究CA IX在食管腺癌組織中的表達,探討在食管癌發(fā)病中的作用,可為臨床診治及預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蛋白的表達情況;應用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分布情況,并分別分析CA IX的表達水平與臨床病理特征的關系。2.應用SPSS 17.0進行統(tǒng)計分析,正態(tài)分布的計量資料用均數(shù)±標準差(X±S)表示,兩組間比較采用t檢驗,重復測量資料采用重復測量數(shù)據(jù)方差分析;計數(shù)資料采用頻數(shù)和比分數(shù)(率)表示,率的比較采用χ2檢驗,表達的關聯(lián)性分析采用Pearson列聯(lián)系數(shù);兩組間比較采用χ2檢驗,配對計數(shù)資料采用配對χ2檢驗;P0.05差異有統(tǒng)計學意義。結果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)計學差異(χ2=41.845,P=0.001)。食管腺癌組織中CAⅨ蛋白的表達與腫瘤浸潤深度、淋巴結轉(zhuǎn)移、分化程度及臨床分期有關(P=0.001),與性別年齡無關(P=0.664)。RT-PCR結果顯示CAⅨ基因在食管不同組織中均有表達,分別為0.217±0.017,0.436±0.03,0.544±0.043,差異有統(tǒng)計學意義(χ2=60.614,P=0.001)。結論CAⅨ蛋白可能參與食管腺癌的發(fā)生發(fā)展,對于CAⅨ蛋白進行檢測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.
【學位授予單位】：鄭州大學
【學位級別】：碩士
【學位授予年份】：2016
【分類號】：R735.1

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