NGAL基因表达上调与大肠肿瘤发生的关系研究  

The Relationship between Upregulation of NGAL and Tumorigenesis of the Colorectum

作　　者：李慧[1] 孙保存[2] 刘志勇[1] 赵秀兰[2] 孙燕[1] 张立华[1] 董学易[1] 齐丽莎[1] 

机构地区：[1]天津市肿瘤防治重点实验室,天津医科大学附属肿瘤医院病理科,天津市300060 [2]天津医科大学病理教研室

出　　处：《中国肿瘤临床》2011年第5期259-262,共4页Chinese Journal of Clinical Oncology

基　　金：国家自然科学基金(编号:30830049);和天津市科技计划项目资助(编号:09ZCZDSF04400)~~

摘　　要：目的:研究大肠腺瘤-腺癌序列过程中中性粒细胞明胶酶相关脂质运载蛋白(NGAL)和基质金属蛋白酶9(MMP-9)表达的变化及相互关系,以阐明其在大肠癌发生发展中的作用。方法:采用组织芯片与免疫组织化学SP法检测94例瘤旁/癌旁组织、92例腺瘤(其中管状腺瘤36例,管状绒毛状腺瘤47例,绒毛状腺瘤9例)、54例腺瘤伴不典型增生或癌变及60例腺癌中NGAL和MMP-9蛋白的表达情况。结果:在大肠腺癌、腺瘤伴不典型增生或癌变、腺瘤、瘤旁/癌旁组织中,NGAL蛋白表达的阳性率分别为55%(33/60)、37%(20/54)、23%(21/92)和2%(2/94),MMP-9蛋白表达的阳性率分别为74%(44/60)、44%(24/54)、25%(23/92)、6%(6/94),NGAL和MMP-9蛋白的表达在腺瘤、腺瘤伴不典型增生或癌变肠腺癌组织中显著高于瘤旁/癌旁组织,差异具有统计学意义(P<0.01),并且在正常肠黏膜→腺瘤→腺瘤伴不典型增生或癌变→腺癌这一过程中两者的表达逐渐增高,差异具有统计学意义(P<0.01),然而二者在腺瘤组中管状腺瘤、管状绒毛状腺瘤、绒毛状腺瘤三者之间的表达差异无统计学意义(P>0.05)。NGAL与MMP-9蛋白的表达在整个序列过程中(正常肠黏膜组、腺瘤组、腺瘤伴不典型增生或癌变组、腺癌组)呈显著正相关(r_8=0.622,P<0.01)。结论:NGAL蛋白和MMP-9蛋白表达的上调可能在大肠腺瘤-腺癌序列的发展过程中发挥一定作用,二者的异常表达可能参与大肠腺癌的发生。Objective： To investigate the expression and relationship of neutrophilic granulocyte gelatinase-associated-lipocalin （ NGAL ） and matrix metalloproteinase-9 （ MMP-9 ） in the colorectal adenoma-carcinoma sequence, and to evaluate their role in the inci- dence of colorectal carcinoma. Methods： The expression of NGAL and MMP-9 proteins were detected using tissue microarray and S-P immunohistochemical methods in 94 cases with formalin-fixed, paraffin-embedded normal paraneoplastic mucosa which were near ade- noma or carcinoma, 92 cases with adenoma （including 36 with tubular adenoma, 47 with tubulovillous adenoma, and 9 with villous adenoma ）, 54 cases with adenoma of atypical hyperplasia, and 60 cases with colorectal adenocarcinoma. Results： The positive expression rates of NGAL protein were 55 % （ 33/60 ）, 37 % （ 20/54 ）, 23 % （ 21/92 ） and 2 % （ 2/94 ） in colorectal adenocarcinoma, adenoma of atypical hyperplasia, adenoma, and normal tissue adjacent to the adenoma or carcinoma, respectively. The positive expression rates of MMP-9 protein were 74 % （ 44/60 ）, 44 % （ 24/54 ）, 25 % （ 23/92 ）, and 6 % （ 6/94 ） in the aforementioned tissues, respectively. The expression of NGAL and MMP-9 proteins was significantly higher in the adenocarcinoma, adenoma of atypical hyperplasia, and adenoma than in the normal paraneoplastic tissue. There were statistical differences among these groups （ P 〈 0.01 ）. The expression of NGAL and MMP-9 proteins increased gradually during the procession from normal mucosa, adenoma and adenoma of atypical hyperplasia to colorectal adenocarcinoma. There were statistically significant differences among the groups （ P 〈 0.01 ）, while there were no statistical differences among tubular adenoma, tubulovillous adenoma and villous adenoma （ P 〉 0.05 ）. There was a significant positive correlation between the expression of NGAL and MMP-9 proteins during the adenoma-carcinoma sequence （ including normal mucosa of the large bowel, aden

关 键 词：中性粒细胞明胶酶相关脂质运载蛋白 基质金属蛋白酶9 大肠 腺癌 腺瘤 

分 类 号：R735.34[医药卫生—肿瘤]