碱基切除修复基因APE和XRCC1表达与大肠癌发生相关性的探讨

目的:通过检测大肠癌、癌旁黏膜与正常黏膜中APE和XRCC1蛋白的表达,探讨大肠癌的发生机制.方法:选取大肠癌手术切除标本185例,其中32例标本取癌旁黏膜组织；正常黏膜组织36例.通过免疫组化方法检测APE和XRCC1蛋白在癌、癌旁黏膜和正常黏膜的表达.结果:大肠癌、癌旁黏膜组APE阳性表达率分别为78.9％(146/185)和81.2％(26/32),两者均明显高于正常黏膜组的61.1％(22/36),x2值分别为5.23和4.86,P值分别为0.024和0.03,但前两者APE表达差异无统计学意义.大肠癌中APE蛋白表达与患者性别、年龄、肿瘤部位、分化程度、浆膜浸润及淋巴结转移无明显相关关系.大肠癌与癌旁黏膜组XRCC1阳性表达率分别为94.6％(175/185)和87.5％(27/32),两者均明显高于正常黏膜组的27.7％(10/36),x2值分别为4.43和29.69,P值分别为0.036和0.002,但前两者间差异无统计学意义.大肠癌中XRCC1蛋白表达与患者性别、年龄、肿瘤部位、分化程度、浆膜浸润及淋巴结转移无明显相关关系.大肠癌XRCC1阳性组的APE阳性率为95.8％(136/142),显著高于大肠癌XRCC1阴性组的86.0％(37/43),XRCC1与APE两者表达呈明显正相关关系,r=0.354,P=0.02.大肠癌和癌旁黏膜组的APE和XRCC1蛋白同时表达的阳性率分别为75.8％(140/185)和65.6％(21/32),两组均明显高于正常黏膜组的16.7％(6/36),x2值分别为46.8和16.17,P值分别为0.001和0.001 5,但癌组与癌旁组间差异无统计学意义.结论:大肠癌和癌旁黏膜中存在APE和XRCC1表达上调.大肠癌发生可能与DNA复制时位点损伤及烷化剂等有毒物质损伤关系密切,同时检测大肠黏膜不同种类DNA修复基因的表达有助于大肠癌的早期诊断.

Discussion for the relationship of expression in base excision repair gene APE and XRCC1 and colorectal carcinoma

OBJECTIVE: To explore BER gene APE,XRCC1’s expression in colorectal carcinoma,adjacent mucosa and normal mucosa,and discuss the relationship between BER and the colorectal carcinoma.METHODS: Colorectal carcinoma specimens were obtained surgically from 185 patients,including adjacent mucosa from 32 patients,normal mucosa from 36 patients.Immunohistochemistry was used to detect the expression of APE,XRCC1 protein in each specimen.RESULTS: In colorectal carcinoma,adjacent mucosa group,the expression of APE were 78.9%(146/185) and 81.2%(26/32),which were much higher than the one in the normal group 61.1%(22/36).The former was(χ2=5.23,P=0.024),the latter was(χ2=4.86,P=0.03),but there’s no significant difference between the former two.There’s no obvious correlation between APE and sex,age,tumor location,differentiation degree,chorion invasion and lymphatic metastasis.In colorectal carcinoma,adjacent mucosa group,the expression of XRCC1 were 94.6%(175/185) and 87.5%(27/32),which were much higher than the one in the normal group 27.7%(10/36),the former was(χ2=4.43,P=0.036),the latter was(χ2=29.69,P=0.002),but there’s no significant difference between the former two.There’s no obvious correlation between XRCC1 and sex,age,tumor location,differentiation degree,chorion invasion and lymphatic metastasis.The expression of APE in positive XRCC1 cases 95.8%(136/142) was much higher than the one in negative XRCC1 cases 86.0%(37/43).There was obvious positive correlation between two of them(r=0.354,P=0.02).The positive rates that APE and XRCC1 expressed simultaneously in colorectal carcinoma,adjacent mucosa were 75.8%(140/185) and 65.6%(21/32),and they were much higher than the one in normal mucosa 16.7%(6/36),the former was(χ2=46.8,P=0.001),the latter was(χ2=16.17,P=0.001 5),but there was no significant difference between them.CONCLUSIONS: The expression rates of APE and XRCC1 are increased in colorectal carcinoma.The expression rates of APE and XRCC1 are increased in colorectal adjacent mucosa.The occurrence of colorectal carcinoma maybe has a close relation with the damage of the site and noxious substance like alkylator in DNA replication.To detect different kinds of expression of DNA repair gene in the same time in colorectal mucosa is helpful to early diagnosis for colorectal carcinoma.