Exploitation of MICA gene polymorphism for development of personalized medicine in oral cancer patients

利用 MICA 基因多态性开发口腔癌患者的个性化医疗

基本信息

批准号：
16592002
负责人：
TANI Ryouji
金额：
$ 2.24万
依托单位：
HIROSHIMA UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2005
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16592002/
关键词：
NK cells MICA gene polymorphism oral cancer disease susceptibility soluble MICA personalized medicine NK activities molecular target antigen MICA遺伝子免疫療法遺伝子多型

项目摘要

The MHC class | chain-related molecule A (MICA) is the ligand of NKG2D, which is activation receptor on most NK cells and antigen-specific effector T cells. These molecules are absent from most cells but can be induced by stress, infection, cell transformation and are frequently expressed in epithelial tumors. The MICA gene has a triplet repeat (GCT) polymorphism in the transmembrane domain, and relevance with the disease susceptibility of Type | -DM. To evaluate the possible association of MICA gene polymorphism with the risk for oral squamous cell carcinoma(OSCC), we analysed MICA polymorphism in cases with OSCC by direct sequencing and fragment analysis.Five distinct MICA alleles A4,A5,A6,A9,and A5.1 were studied. MICA 5.1 variant gene contains a fournucleotide insertion that causes a stop codon in the transmembrane region. In addition, as an sMICA has been considered to cause the down regulation of NKG2D resulted in suppression of NK cells and antigen-specific effector Tcells, we have examined the concentration of soluble MICA(sMICA) in the serum of OSCC patients by ELISA assay.As the result, we have found that the phenotype frequency of allele 5.1 of MICA and the sMICA levels in subjects with OSCC were significantly higher than those in controls.These results suggested that susceptibility to OSCC is linked to the MICA microsatellite and A5.1 allele might confer the risk of OSCC.

MHC类|与链相关的分子A（MICA）是NKG2D的配体，它是大多数NK细胞和抗原特异性效应T细胞的活化受体。这些分子不含大多数细胞，但可以由压力，感染，细胞转化诱导，并且在上皮肿瘤中经常表达。云母基因在跨膜结构域中具有三联体重复（GCT）多态性，并且与类型的疾病敏感性相关。 -dm。为了评估云母基因多态性与口服鳞状细胞癌（OSCC）的风险的可能关联，我们研究了通过直接测序和片段分析的OSCC分析云母多态性的。云母5.1变体基因包含一个四核苷酸插入，该插入在跨膜区域引起终止密码子。此外，由于已经认为SMICA会导致NKG2D的下调导致NK细胞和抗原特异性效应TCELLS抑制，因此我们检查了ELISA分析中OSCC患者血清中可溶性云母（SMICA）的浓度。由于结果，我们发现了SMICA和SMICA的频率更高的SMICA和SMICA级别。控制。这些结果表明，对OSCC的敏感性与云母微卫星有关，而A5.1等位基因可能会赋予OSCC的风险。