p53基因突变对大肠肿瘤原位Th1/Th2平衡的影响

Effects of p53 gene mutations on the balance of helper T cell 1 with helper T cell 2 in colorectal tumors

目的 :评价 p5 3突变对大肠腺瘤和大肠癌局部辅助T细胞 (Th) 1/Th2平衡的影响 ,进而探讨p5 3突变促进大肠癌发生的免疫学机制。方法 :研究对象包括大肠腺瘤 30例、大肠癌 38例 ,癌旁正常黏膜 6 8例作为对照组。应用PCR SSCP银染法结合测序检测p5 3基因 5～ 8外显子突变 ,采用酶联免疫吸附试验 (ELISA)检测肠组织培养上清液中 4种细胞因子 (IL 2、IL 4、IL 10和IFN γ)水平。结果 :p5 3突变阳性组培养上清的IL 2、IFN γ水平低于阴性组和对照组 (P <0 0 1) ,而IL 10则高于阴性组及对照组 (P <0 0 5 ) ,各组IL 4水平未显示差异 (P >0 0 5 )。结论 :p5 3突变引起原位Th1/Th2平衡失调 ,表现为由Th1向Th2漂移。初步推断 ,p5 3基因失活在大肠癌发生的免疫学机制中可能具有重要作用。

Purpose To evaluate the effects of p53 gene mutations on the balance of T helper cell 1 (Th1) with T helper cell 2 (Th2) in colorectal adenoma and carcinoma, and to further study the immunological mechanism of p53 gene mutations promoting the colorectal cancer formation. Methods Endoscopic colorectal mucosal biopsies were taken from 68 patients with colorectal tumors,including adenomas( n =30) and carcinomas ( n =38),and their normal mucosa served as normal controls ( n =68).PCR SSCP analysis with silver staining was used to detect mutations in exons 5～8 of p53 gene,followed by sequencing. Four cytokines (IL 2,IL 4,IL 10,IFN γ) were detected by enzyme linked immunosorbent assay (ELISA) with the culture supernatants of colorectal tissue. Results IL 2 and IFN γ levels in culture supernants of positive group were lower ( P< 0 01),in contrast,IL 10 levels higher ( P< 0 05) than those of negative group and normal controls, but there was no difference of IL 4 levels among all groups ( P> 0 05). Conclusions p53 gene mutations induce inbalance of local Th1 and Th2 levels, showing a drift from Th1 to Th2. p53 gene inactivation may play a critical role in immunological mechanism of colorectal carcinogenesis.