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MAGE-A3基因单核苷酸多态性及其在中国非小细胞肺癌(NSCLC)患者中的临床意义

Single nucleotide polymorphisms of MAGE-A3 gene and its clinical implications in Chinese patients with non-small cell lung cancer (NSCLC).

作者信息

Yang Xue-Ning, Huang Ling, Chen Yu, An She-Juan, Zhang Xu-Chao, Liao Ri-Qiang, Su Jian, Wu Yi-Long

机构信息

Guangdong Lung Cancer Institute, Guangdong Provincial Key Laboratory of Translational Medicine in Lung Cancer, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangzhou 510080, China.

出版信息

Chin J Cancer Res. 2015 Jun;27(3):301-8. doi: 10.3978/j.issn.1000-9604.2014.11.03.

Abstract

BACKGROUND

Available study revealed advanced tumors have a higher expression rate of MAGE-A3 gene which has a lot of single nucleotide polymorphism (SNP) loci with polymorphisms. This study aimed to analyze the allele frequency of SNP loci in MAGE-A3 gene and investigate the relationship between MAGE-A3 gene polymorphisms and clinical factors.

METHODS

Tumor samples of a cohort of 191 NSCLC patients were collected. EGFR mRNA expression were detected by qRT-PCR. SNPs in whole length of MAGE-A3 gene were detected by direct sequencing. Frequencies of the SNPs were correlated to gene expression, mutation status of EGFR and clinical factors.

RESULTS

Sequencing analysis confirmed that allele frequencies of genotypes on SNP loci rs5970360, rs5925210, rs5970361, rs5925211 and rs35123853 were CC (0.681)/CT (0.319), CC (0.660)/CG (0.340), CC (0.681)/CA (0.319), AA (0.984)/AT (0.016) and GG (1.000)/GA (0.000), respectively, which were different from the frequencies and genotypes of MAGE-A3 in SNP database. Chi-square tests showed the EGFR mRNA expression level had significant correlation with the genotypes of SNP loci rs5970360 and rs5925210. But all frequencies of each MAGE-A3 SNPs were not found significantly different between EGFR mutant and wild type patients. MAGE-A3 gene polymorphisms had no significant effects on survival of NSCLC patients.

CONCLUSIONS

Chinese patients with NSCLC had different SNP patterns of MAGE-A3 in comparison with those in international SNP database. These MAGE-A3 SNP loci might have not prognostic significance. MAGE-A3 SNP loci rs5970360 and rs5925210 might be predictive for EGFR mRNA expression levels and helpful to the selection of patients for epidermal growth factor receptor (EGFR) targeted immunotherapy.

摘要

背景

现有研究表明,晚期肿瘤中MAGE - A3基因的表达率较高,该基因存在许多具有多态性的单核苷酸多态性(SNP)位点。本研究旨在分析MAGE - A3基因中SNP位点的等位基因频率,并探讨MAGE - A3基因多态性与临床因素之间的关系。

方法

收集191例非小细胞肺癌(NSCLC)患者的肿瘤样本。通过qRT - PCR检测EGFR mRNA表达。采用直接测序法检测MAGE - A3基因全长的SNP。将SNP的频率与基因表达、EGFR突变状态及临床因素进行相关性分析。

结果

测序分析证实,SNP位点rs5970360、rs5925210、rs5970361、rs5925211和rs35123853基因型的等位基因频率分别为CC(0.681)/CT(0.319)、CC(0.660)/CG(0.340)、CC(0.681)/CA(0.319)、AA(0.984)/AT(0.016)和GG(1.000)/GA(0.000),与SNP数据库中MAGE - A3的频率和基因型不同。卡方检验显示,EGFR mRNA表达水平与SNP位点rs5970360和rs5925210的基因型显著相关。但在EGFR突变型和野生型患者中,各MAGE - A3 SNP的所有频率均无显著差异。MAGE - A3基因多态性对NSCLC患者的生存无显著影响。

结论

与国际SNP数据库相比,中国NSCLC患者的MAGE - A3基因具有不同的SNP模式。这些MAGE - A3 SNP位点可能无预后意义。MAGE - A3 SNP位点rs5970360和rs5925210可能对EGFR mRNA表达水平具有预测作用,有助于表皮生长因子受体(EGFR)靶向免疫治疗患者的选择。

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