原发性肝癌患者CXCR1、CXCR2及CXCL8的表达及其临床意义  

Expression and clinical significance of CXC chemokine receptors 1 and 2 and CXCL8 in primary hepatocellular carcinoma

作　　者：毕惠娟[1] 陈建民[1] 陈静静[1] 王健[2] 

机构地区：[1]安徽医科大学第四附属医院检验科,合肥230000 [2]安徽理工大学病原学与免疫学教研室,淮南232001

出　　处：《中华微生物学和免疫学杂志》2017年第7期545-551,共7页Chinese Journal of Microbiology and Immunology

基　　金：安徽医科大学校级基金（2015xkj049）;安徽省自然科学基金（1308085MH148）;安徽省教育厅重大自然科学研究项目（KJ2016SD20）

摘　　要：目的通过检测原发性肝癌（primary hepatocellular carcinoma，PHC）患者外周血单个核细胞及肝活检组织CXC趋化因子受体1（CXCR1）、CXCR2及CXC趋化因子配体8（CXCL8）表达，探讨其在PHC中的临床意义。方法抽取36例临床确诊PHC患者、30例肝硬化患者及28例健康体检者血液，用实时荧光定量PCR法检测PBMCs中CXCR1、CXCR2及CXCL8mRNA水平，分析CXCR1、CXCR2及CXCL8水平与PHC患者临床病理特征及预后的关系；SP法检测肝组织CXCR1、CXCR2及CXCL8蛋白表达水平；化学发光免疫分析法检测受试者血清C反应蛋白（CRP）、甲胎蛋白（AFP）及铁蛋白（FER）水平，并对各指标进行相关性分析。结果PHC组PBMCs内CXCR1、CXCR2及CXCL8mRNA均明显高于正常对照组，差异有统计学意义（P〈0．01）；PHC组CXCR1、CXCR2及CXCL8mRNA结果均高于肝硬化组，且差异有统计学意义（P〈0．05）。PHC组CXCR1、CXCB2及CXCL8分别与肿瘤浸润深度、有无淋巴结转移或远处转移、TNM分期及血清CRP、AFP及FER水平有关（P〈0．05），其他指标之间无相关关系。SP结果提示，PHC组CXCR1、CXCR2及CXCL8蛋白水平也较对照组升高。结论PHC患者PBMCs及肝活检组织CXCR1、CXCR2及CXCL8表达明显升高，且与血清CRP、AFP及FER呈正相关，推测CXCRl、CXCR2及CXCL8介导的信号转导过程可能在原发性肝癌发生发展中发挥重要作用，为肝癌免疫干扰治疗提供新的靶点。Objective To investigate the expression and clinical significance of CXC chemokine receptors 1 and 2 （ CXCR1 and CXCR2） and CXCL8 in peripheral blood mononuclear cells （PBMCs） and liver biopsy tissues from patients with primary hepatocellular carcinoma （ PHC ）. Methods Serum speci- mens were collected from 36 patients with PHC, 30 patients with liver cirrhosis and 28 healthy subjects. Quantitative real-time polymerase chain reaction （ qRT-PCR ） was performed to measure the expression of CXCR1, CXCR2 and CXCL8 at mRNA level in PBMCs. Streptavidin-perosidase （SP） immunobistochemis- try was used to detect the expression of CXCR1, CXCR2 and CXCL8 at protein level in liver biopsy tissues. Levels of C-reactive protein （CRP） , alpha-fetoprotein （AFP） and ferritin （FER） in the serum specimens were detected by chemiluminescence immunoassay. Then the correlations between these markers were analyzed. Results All of the resuhs showed that the expression of CXCR1, CXCR2 and CXCL8 at mRNA level in PBMCs from the PHC group were higher than those of the healthy control group （ P〈0.01 ） as well as those of the liver cirrhosis group （ P〈O. 05 ）. Up-regulated expression of CXCR1, CXCR2 and CXCL8 in pa- tients with PHC were associated with the depth of tumor invasion, lymph node or distant metastasis, clinical stage and levels of CRP, AFP and FER in serum （ P 〈 0.05 ）. The expression of CXCR1, CXCR2 and CXCL8 at protein level in liver biopsy tissues were also significantly increased in the PHC group in comparison with those of the healthy control group as indicated by the result of SP immunohistochemistry （ P 〈 O. 05）. Conclusion Levels of CXCR1, CXCR2 and CXCL8 in the patients with PHC are significantly in- creased and positively correlated with the levels of AFP, FER and CRP in serum, suggesting that the signal transduction process mediated by CXCR1, CXCR2 and their common ligand CXCL8 may play a key role in the pathological process of PHC. This study may provide a potential

关 键 词：原发性肝癌 CXCR1 CXCR2 CXCL8 mRNA 甲胎蛋白 铁蛋白 C反应蛋白 

分 类 号：R730.43[医药卫生—肿瘤] R735.7[医药卫生—临床医学]