106例大肠癌病人HLA、MICA基因频率分布及sMICA表达水平与癌发生的相关性研究  

Preliminary Study on the HLA / MICA Gene Frequencies Distribution and sMICA Expression Levels in Colorectal Cancer Patients from 106 Cases

作　　者：杨劭宇[1] 黄颖烽[1] 谭茵[2] 魏亚明[1] 彭吉祥[1] 罗宏图[1] 肖灿军[3] 

机构地区：[1]广州医学院附属广州市第一人民医院普外科,广东广州510180 [2]广州医学院基础学院生化实验中心,广东广州510182 [3]广州医学院研究生院,广东广州510182

出　　处：《热带医学杂志》2013年第2期178-182,共5页Journal of Tropical Medicine

基　　金：广东省自然科学基金(9151006001000009);广州市医药卫生科技重点项目(20121A021008)

摘　　要：目的初步探讨人类白细胞抗原(HLA)和主要组织相容性复合体Ⅰ类链相关蛋白A(MICA)基因遗传免疫因素及其可溶性MICA(sMICA)表达水平与广东地区大肠癌的相关性。方法采用直接测序法对106例确诊为大肠癌的患者和118名健康献血者进行HLA及MICA基因高分辨分型。应用PyPopWin32统计HLA及MICA各等位基因频率,应用SPSS16.0和Helixtree分析软件进行HLA-MICA基因与肿瘤的免疫遗传关联分析。应用生物素/亲和素ELISA酶联免疫(BA-ELISA)法进行血清中sMICA浓度检测,应用特征曲线(ROC)对sMICA结果进行分析与评价。结果病例组血清中sMICA平均水平为(0.92±0.75)ng/ml,对照组血清中平均水平为(0.29±0.33)ng/ml;病例组sMICA的浓度水平明显高于对照组,差异具有统计学意义(P<0.0001)。ROC曲线下面积为0.816,sMICA的临床诊断界点为0.302ng/ml。HLA-A*02:01为大肠癌风险等位基因;未发现与MICA关联的风险等位基因;HLA-B与MICA位点连锁不平衡的存在具有大肠癌免疫遗传相关风险单倍型的可能。结论对大肠癌病人及具有相同遗传背景的人群在术前可找出高危基因人群,并对其进行可溶性MICA筛选,以达到大肠癌极早期诊断的目标。Objective To evaluate the association of colorectal cancer with MICA gene expression level in patients sera and investigation of the genetic immunological background of MICA and HLA gene families in patients. Methods 106 patients with eolorectal cancer and 118 healthy controls the HLA and MICA alleles were identified by SBT. The gene frequency was analyzed by PyPopWin32 software. SPSS16.0 and Helixtree were used to analysis the association of cancer with MICA and HLA allelic frequency and linkage disequilibrium. Both of them were tested the soluble MICA （sMICA） concentration in sera by ELISA method. The sMICA level were assessed the value by ROC curve. Results In patient group, the linkage disequilibrium with HLA-B and MICA showed the strong relation to the colorectal cancer. The average sMICA level was significantly higher in patients （0.92~0.75）ng/ml than in controls （0.29＋0.33）ng/ml, P〈0.0001. In this article, the area of ROC curve was 0.797, and sMICA diagnostic cutoff point was 0.302 ng/ml. HLA-A ＊02：01 was the high risk factor of colorectal cancer. No risks associated MICA allele was found. The presence of HLA-B and MICA locus linkage disequilibrium with colorectal cancer immune genetic risk haplotype was possible. Conclusion It is the first time of high-resolution genotyping and assoeiation analysis and serum of sMICA detection of the patients with colorectal cancer in Guangdong. We can promptly identify the high risk group in preoperative colorectal cancer patients with the same genetic background, and perform sMICA screening to achieve the goal of very early diagnosis of eolorectal cancer.

关 键 词：可溶性MICA 大肠癌 HLA MICA 

分 类 号：R735.34[医药卫生—肿瘤]