结肠癌中心和边缘组织增殖能力的差异及相关基因的表达  

Difference of tumor cell proliferative capability and the interrelated genes'expression in the center and edge tissues of colon cancer

作　　者：郭洁[1] 沈志祥[1] 罗和生[1] 滕小军[1] 王晓玲[1] 

机构地区：[1]武汉大学人民医院消化内科,430060

出　　处：《中华消化杂志》2005年第12期720-724,共5页Chinese Journal of Digestion

摘　　要：目的探索结肠癌组织不同区域肿瘤细胞是否存在增殖能力的差异,且这种区域性差异和多重抑癌基因 p16及其可变读码框架 p14基因的表达情况及其甲基化状态的相关性。方法免疫组化法测定癌块不同区域增殖蛋白 Ki67和 P16、P14的表达差异,激光显微切割技术结合甲基化特异性PCR、巢式逆转录 PCR 观察同一癌块不同区域癌细胞 p16及 p14基因甲基化状态的改变及其 mRNA 的表达情况。结果在42份癌组织标本的中心,增殖蛋白 Ki67均呈强阳性表达,而 P16和 P14蛋白表达缺失;在癌组织标本的边缘,有13份 Ki57表达阳性(30.1%)。不同区域癌细胞的增殖能力差异有统计学意义(P<0.05),且与年龄、性别、Dukes 分期、p14的表达无关,但与 p16的表达显著相关(x^2=25.37.P<0.01)。且 p16基因的甲基化状态和 mRNA 的表达也存在明显的区域性差异(P<0.05)。结论人结肠癌组织中存在肿瘤细胞增殖能力的区域性差异,在癌组织边缘肿瘤细胞侵袭力增强的同时增殖能力下降,癌边缘区 p16基因去甲基化后的再表达可能是这一细胞事件的分子原因。Objective To investigate the difference of tumor cell proliferation between the center and the edge tissues of human colon cancer and its relationship with the expression and methylation of p16 and p14 gene. Methods The expression of Ki67, P14 and P16 protein was assessed by immunohistochemistry, methylation status and mRNA expression of p16 and p14 gene in different area of colon cancer tissue were analyzed by methylation-specific PCR, RT-PCR and microdissection technique. ResultsThere was significant difference in expressions of Ki67 between the center（100. 0%） and the edge （30.1%） tissue in 42 cases of colon cancer（P〈0. 05）, but no expression of P14 and P16 protein. In central tissue the difference did not correlate with age, gender, Dukes staging, the expression of p14 gene, but there was correlate with the expression of p16 gene（X^2= 25.37, P〈0.01）. The methylation status and the mRNA expression of p16 gene had significant difference in tumor cells of different areas of colon cancer（P〈0. 05）. Conclusions In the edge tissue of human colon cancer, the proliferation of tumor cells was in decrease while the invasion was trended to increase. The re-expression of p16 gene after demethylation in the edge tissue of colon cancer might be attributed to this event.

关 键 词：结肠肿瘤 基因 p16 基因 p14 激光显微切割技术 甲基化 

分 类 号：R735.35[医药卫生—肿瘤]