食管腺癌组织中CAIX蛋白的表达及其临床意义

发布时间：2018-11-19 18:00

【摘要】：背景与目的食管癌(Esophageal cancinoma,EC)是常见的消化道实体恶性肿瘤,在所有恶性肿瘤占2%,居全球第七位,是我国最常见的六大肿瘤之一。食管腺癌(esophageal adenocarcinoma,EAC)是食管癌常见的病理类型之一,在西方国家以食管腺癌为主,在我国食管腺癌的发病率仅次于食管鳞状细胞癌(Esophageal squamous cell carcinoma,ESCC)。在中国原发食管腺癌的发病率占食管癌的5%-10%;食管腺癌患者的五年生存率约为10%,手术后的五年生存率较非手术的高,手术后约为15%-40%。全世界每年死于食管癌的人约30万,但我国约占15万。据预测,癌症的死亡率还在持续增长,到2030年估计将有1.1亿人死于癌症。目前,包括中国在内的世界性范围内,食管腺癌发生率呈逐年明显升高的趋势。虽有研究表明,早期食管癌患者行手术根治术可以达到满意效果,但因为早期症状不明显、特异性不高,而且大多数患者在发病早期进食哽咽感、胸骨后疼痛等不在意,因此初诊时多数患者就已经进入中晚期。对于食管腺癌的诊疗来说,探索寻求一种新的方法和思路非常重要。目前,食管癌的治疗有多种手段,最主要方式是采用外科手术方法(病变组织切除并作消化道重建),依据实际情况配合放化疗、生物免疫治疗、中医中药等综合治疗。以上方法作为传统的治疗方式,但是对于不能行根治手术的晚期患者,特别是不能耐受手术,生活质量和生存期得不到明显改善,不能耐受治疗副作用出现病情加重甚至死亡。因此,对于食管癌来说,寻求探索研发一种新型的、有效的诊疗方法十分必要。随着技术的进步,DNA重组技术的逐步完善,肿瘤的免疫靶向治疗技术也在快速发展,在未来有可能成为主要的诊疗手段。食管癌是常见消化系统恶性肿瘤之一,其发病是多阶段、多因素、多基因共同作用的结果,研究其发病机制对食管癌的诊断及治疗意义重大。本研究针对CA IX在食管腺癌中表达情况进行研究,探讨食管腺癌的发病机理,为靶向治疗提供研究基础。碳酸酐酶IX(carbonic anhydras IX,CA IX)为一个跨膜蛋白,已为肿瘤相关蛋白,主要在正常人上消化道及胰腺、胆囊、肝脏等相关器官中表达,其他正常组织几乎不表达,而在许多实体瘤中高度表达,并参与肿瘤细胞的增殖、转移和侵袭相关。CA IX对放疗及化疗产生耐受,且促使恶化,加快癌细胞增殖与转移。快速生长的肿瘤细胞促使氧化磷酸化、无氧酵解等,使肿瘤微环境改变易缺血、缺氧。CA IX使肿瘤细胞内碱外酸,这为肿瘤的生长、转移和侵袭创造了条件。CAⅨ蛋白在国内对于腺癌的研究甚少,而且目前关于CA IX在食管腺癌组织中的表达情况国内尚无报告。因此,研究CA IX在食管腺癌组织中的表达,探讨在食管癌发病中的作用,可为临床诊治及预后判断提供新的理论依据。方法1.采用免疫组化SP的方法检测45例食管腺癌组织、癌旁不典型增生及正常食管组织中CA IX蛋白的表达情况;应用RT-PCR方法分析在食管腺癌组织、癌旁不典型增生及正常食管组织中表达分布情况,并分别分析CA IX的表达水平与临床病理特征的关系。2.应用SPSS 17.0进行统计分析,正态分布的计量资料用均数±标准差(X±S)表示,两组间比较采用t检验,重复测量资料采用重复测量数据方差分析;计数资料采用频数和比分数(率)表示,率的比较采用χ2检验,表达的关联性分析采用Pearson列联系数;两组间比较采用χ2检验,配对计数资料采用配对χ2检验;P0.05差异有统计学意义。结果CAⅨ蛋白在食管腺癌组织、癌旁不典型增生和正常食管组织中的阳性表达率依次为66.7%(30/45),24.4%(11/45),4.4%(2/45),三者两两比较具有统计学差异(χ2=41.845,P=0.001)。食管腺癌组织中CAⅨ蛋白的表达与肿瘤浸润深度、淋巴结转移、分化程度及临床分期有关(P=0.001),与性别年龄无关(P=0.664)。RT-PCR结果显示CAⅨ基因在食管不同组织中均有表达,分别为0.217±0.017,0.436±0.03,0.544±0.043,差异有统计学意义(χ2=60.614,P=0.001)。结论CAⅨ蛋白可能参与食管腺癌的发生发展,对于CAⅨ蛋白进行检测有助于食管腺癌的诊断治疗。
[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.
【学位授予单位】：郑州大学
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：R735.1

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