中国汉族人群中KIR3DL1及其配体对宫颈癌的保护性作用及机制探讨  

A protective effect conferred by KIR3DL1 and its cognate ligand against cervical cancer among ethnic Han Chinese population and its potential mechanism

作　　者：甄建新[1] 朱雷雷 李卫红[2] 胡海燕[2] 邓志辉[3] 熊礼宽[1] Zhen Jianxin;Zhu Leilei;Li Weihong;Hu Haiyan;Deng Zhihui;Xiong Likuan(Central Laboratory,Shenzhen Baoan Maternal and Child Health Hospital,Shenzhen,Guangdong 518133,China;Department of Gynecology,Shenzhen Maternity and Child Healthcare Hospital,Shenzhen,Guangdong 518017,China;Institute of Blood Transfusion,Shenzhen Blood Center,Shenzhen,Guangdong 518035,China)

机构地区：[1]广东省深圳市宝安区妇幼保健院中心实验室,518133 [2]广东省深圳市妇幼保健院妇科,518017 [3]广东省深圳市血液中心输血医学研究所,518035

出　　处：《中华医学遗传学杂志》2019年第10期1035-1038,共4页Chinese Journal of Medical Genetics

基　　金：深圳市科技创新委员会项目(JCYJ20160429172728335).

摘　　要：目的探讨中国汉族人群抑制性KIR(inhibitory KIR,iKIR)受体及其HLA配体在宫颈癌发生发展中的作用及其机制.方法随机采集265例宫颈上皮内瘤样病变和宫颈癌患者及200名正常女性的外周血样本,应用特异性PCR扩增、反向序列特异性寡核苷酸探针、序列分型方法以及TCGA数据库的宫颈癌数据,分别分析iKIR基因及其受配体基因组合、肿瘤组织iKIR转录水平、KIR3DL1等位基因与宫颈癌发生发展的相关性.结果在4种iKIR基因(KIR2DL1、2DL2/3、3DL1和3DL2)中,正常人群KIR3DL1基因和KIR3DL1+HLA-Bw4基因组合的检出频率均显著高于宫颈癌患者(96.5%vs.87.0%、81.5%vs.64.8%),差异有统计学意义(P=0.018,P=0.009);肿瘤组织KIR3DL1高转录水平的富颈癌患者生存率显著高于KIR3DL1低/中转录水平的宫颈癌患者,差异有统计学意义(P=0.028);正常人群强抑制性高表达型KIR3DL1*01502等位基因的检出频率显著高于宫颈癌患者(76.0%vs.59.3%),差异有统计学意义(P=0.015).结论汉族人群中KIR3DL1及其受-配体组合对拮抗宫颈癌发生发展具有保护性作用,其保护作用可能与强抑制性高表达型KIR3DL1*01502等位基因有关.Objective To explore the role of inhibitory KIR(iKIR)and its cognate HLA ligand in the occurrence and development of cervical cancer among ethnic Han Chinese and its potential mechanism.Methods Peripheral blood samples from 265 Han Chinese patients with cervical intraepithelial neoplasia(CIN)/cervical cancer and 200 ethnically matched healthy controls were collected.The results of KIR PCR-SSP,HLA PCR-rSSO and KIR3DL1 PCR-SBT,together with cervical cancer data from the TCGA database,were used to assess the association of iKIR genes,receptor-ligand gene combinations,iKIR transcription level in the tumor tissue and the KIR3DL1 alleles with the occurrence and development of cervical cancer.Results Among the four iKIR genes(KIR2DL1,2DL2/3,3DL1 and 3DL2),the frequencies of KIR3DL1 and KIR3DL1-HLA-Bw4 genes among controls were significantly higher than those of the cervical cancer group(96.5%vs.87.0%,P=0.018;81.5%vs.64.8%,P=0.009).The survival rate of cervical cancer patients with a high transcription level of KIR3DL1 in tumor tissues was significantly higher than those with a low/medium transcription level(P=0.028).The frequency of strong-inhibitory and high-expression KIR3DL1*01502 allele among the healthy population was significantly higher than that of the cervical cancer group(76.0%vs.59.3%,P=0.015).Conclusion Combined KIR3DL1 and KIR3DL1-HLA-Bw4 can confer a protective effect against the development of cervical cancer,which may be attributed to the strong-inhibitory and high-expression allele of KIR3DL1*01502.

关 键 词：宫颈癌 抑制性KIR KIR3DL1 测序分型 转录水平 

分 类 号：R737[医药卫生—肿瘤]