Survivin蛋白表达和hMLH1基因启动子甲基化与结直肠癌的关系研究

发布时间：2018-05-23 17:49

本文选题：survivin + hMLH1　；参考：《吉林大学》2017年硕士论文

【摘要】：目的:研究结直肠癌中survivin蛋白的表达情况,h MLH1基因启动子的甲基化情况,以及二者与结直肠癌的形成、侵润和预后的关系。资料与方法:选取行根治手术的结直肠癌患者45例(术后病理诊断明确,切缘为阴性;患者在手术之前,未行任何抗肿瘤治疗),分别进行5年术后随访。对照组:挑取出相应患者距癌灶5厘米以上的结直肠正常组织45例(术后病理诊断明确)。分别于吉林大学第一医院病理科及组织标本库,找到患者对应的标本蜡块及新鲜冻存组织。按照患者年龄、性别、癌灶发生位置、T分期、分化程度、淋巴结转移情况、脉管侵润等有关临床基本资料来分组。分别利用免疫组织化学方法(IHC法)及甲基化特异性PCR方法(MSP法),测定survivin蛋白的表达及h MLH1基因启动子甲基化情况。用SPSS 22.0等软件分析。结果:1.结直肠癌survivin蛋白的阳性表达比例为64.44%(29/45),显著大于正常结直肠中的阳性表达比例8.89%(4/45),差异有意义(P0.001),并且与T分期、分化程度及淋巴结转移情况有关(P0.05),而和年龄、性别、癌灶发生位置、脉管侵润无关(P0.05)。2.结直肠癌h MLH1基因启动子的甲基化比例是35.56%(16/45),正常结直肠组织中未发现甲基化,差异有意义(P0.001),并且与肿瘤分化程度有关(P=0.001),而与患者年龄、性别、癌灶发生位置、T分期、淋巴结转移情况、脉管侵润等不相关(P0.05)。3.结直肠癌survivin蛋白的表达和h MLH1基因的甲基化情况,两者表现为正相关关系(r=0.358,p=0.016)。4.结直肠癌中,survivin蛋白阳性、阴性患者术后5年的生存率各为27.53%、65.45%。survivin蛋白阴性患者,其术后生存情况显著比阳性患者好(P=0.006)。5.结直肠癌中,h MLH1基因启动子甲基化、非甲基化患者的术后5年生存率分别是25.00%、50.78%,非甲基化患者的术后生存情况要好于甲基化患者(P=0.037)。结论:1.Survivin蛋白在结直肠癌中的表达显著高于正常组织,且与肿瘤T分期、分化程度及淋巴结转移情况相关。2.h MLH1基因启动子在结直肠癌中发生甲基化情况明显高于正常组织,且与肿瘤分化程度相关。3.结直肠癌中survivin蛋白的表达及h MLH1基因启动子甲基化,两者呈正相关。4.Survivin蛋白高表达及h MLH1基因启动子甲基化和结直肠癌的不良预后相关。
[Abstract]:Aim: to investigate the expression of survivin protein in colorectal cancer and the relationship between the methylation of the promoter of h MLH1 gene and the formation, invasion and prognosis of colorectal cancer. Materials and methods: a total of 45 patients with colorectal cancer underwent radical resection with definite pathological diagnosis and negative margin were followed up for 5 years without any antitumor therapy before operation. Control group: 45 patients with normal colorectal tissue more than 5 cm from the cancer focus were removed. The paraffin and fresh frozen tissue of the patients were found in the pathology department and tissue specimen bank of the first Hospital of Jilin University. Patients were classified according to age, sex, location and T stage, differentiation, lymph node metastasis and vascular invasion. The expression of survivin protein and the promoter methylation of h MLH1 gene were determined by immunohistochemistry and methylation specific PCR. SPSS 22.0 and other software analysis. The result is 1: 1. The positive rate of survivin protein expression in colorectal cancer was 64.44 / 29 / 45, which was significantly higher than that in normal colorectal cancer (8.89 / 45 / 45). The difference was significant (P 0.001), and it was related to T stage, differentiation and lymph node metastasis, and to age, sex, location of cancer focus. The vascular invasion was not related to P0.05. 2. The methylation ratio of h MLH1 promoter in colorectal cancer was 35.56 / 16 / 45. There was no methylation in normal colorectal tissues. The difference was significant (P 0.001), and it was related to the degree of tumor differentiation, but to the age, sex, location and stage of cancer. Lymph node metastasis, vascular invasion and other unrelated P0.05. 3. The expression of survivin protein and the methylation of h MLH1 gene in colorectal cancer showed a positive correlation between 0.358 and 0.016. 4. The 5-year survival rate of patients with negative colorectal cancer was 27.53 and 65.45, respectively. The survival rate of patients with negative survivin protein was significantly higher than that of patients with positive prognosis. In colorectal cancer, the 5-year survival rate of patients with MLH1 promoter methylation and demethylation was 25.00 and 50.78, respectively. The survival rate of non-methylated patients was better than that of methylated patients. Conclusion the expression of survivin protein in colorectal cancer is significantly higher than that in normal tissues, and the methylation of MLH1 gene promoter in colorectal cancer is significantly higher than that in normal tissues, which is related to tumor T stage, differentiation degree and lymph node metastasis. And related to the degree of tumor differentiation. 3. There was a positive correlation between the expression of survivin protein and the methylation of h MLH1 gene promoter in colorectal cancer. 4. The overexpression of survivin protein and the methylation of h MLH1 gene promoter were correlated with the poor prognosis of colorectal cancer.
【学位授予单位】：吉林大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R735.34

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