贲门腺癌组织中RKIP表达变化及其与血清NF-κB p65蛋白、T淋巴细胞亚群的关系

Expression changes of Raf kinase inhibitor protein in gastric cardia adenocarcinoma and its relationships with NF-κB p65 and T-lymphocyte subsets

目的观察Raf激酶抑制蛋白(RKIP)在贲门腺癌组织中的表达变化,进一步探讨贲门腺癌的发生、发展机制。方法收集160例贲门腺癌患者(腺癌组)的腺癌组织及其癌旁组织,应用免疫组织化学SP法检测RKIP表达;采用ELISA法和流术细胞术分别检测腺癌组和50例查体健康者(对照组)的血清NF-κB p65蛋白、T淋巴细胞亚群水平。采用Spearman秩和相关分析法分析指标间的关系。结果贲门腺癌及癌旁组织中RKIP表达阳性率分别为38.7%、52.5%(P<0.05),在有、无淋巴结转移者中的表达阳性率分别为24.4%、53.1%(P<0.05,t=4.34);腺癌组血清总NF-κB p65蛋白水平高于对照组(P<0.05),但RKIP表达阳性与阴性者水平无显著差异(P>0.05),有淋巴结转移者高于无淋巴结转移者(P<0.05);腺癌组细胞免疫功能低于对照组,尤以RKIP表达阴性者为著(P<0.05)。结论 RKIP在贲门腺癌组织中表达降低并与肿瘤发生、发展、浸润转移有关,可能机制为抑制NF-κB活性及细胞免疫功能,使肿瘤细胞逃避机体的免疫监视。

Objective To observe the expression changes of Raf kinase inhibitor protein （ RKIP） in gastric cardia ad-enocarcinoma （ GCA） and analyze the relationships with nuclear factor （ NF）-κB p65 activity as well as the lymphocyte im-mune function , further to investigate the mechanisms of occurrence and development of GCA .Methods The expression of RKIP in the cancerous tissues and paracancerous tissues from 160 GCA patients （ carcinoma group ） was examined by im-munohistochemical SP method .The levels of NF-κB p65 and T-lymphocyte subsets expressed in the serum of carcinoma group and 50 healthy people （ control group ） were measured by ELISA and flow cytometry .The relationships among differ-ent indexes were analyzed by Spearman rank correlation analysis method .Results The positive expression ratios of RKIP in the cancerous tissues and paracancerous tissues were 38.7% and 52.5 %, respectively （ P〈0.05）; the positive ex-pression ratios of RKIP in lymph node and non-lymph node metastasis patients were 24.4%and 53.1 %, respectively （P〈0.05, t=4.34）;and the total level of NF-κB p65 secreted in the carcinoma group was significantly higher than that of the control group （P〈0.05）, but there was no significant difference between the patients with positive and negative ex -pression of RKIP （P〉0.05）.The expression of active NF-κB p65 was significantly higher in the GCA patients with lym-phatic metastasis as compared with the patients without lymphatic metastasis （P〈0.05）.The immune function in the car-cinoma group was significantly decreased as compared with that of the control , especially in patients with negative expres-sion of RKIP （P〈0.05）.Conclusion The RKIP expression is down-regulated in the GCA tissues, which is associated with the occurrence , development and invasion of GCA by preventing the activation of NF-κB and lymphocyte immune func-tion, leading to the tumor cells evading from immune surveillance .