南方医科大学学报

南方医科大学学报 ›› 2020, Vol. 40 ›› Issue (10): 1373-1379.doi: 10.12122/j.issn.1673-4254.2020.10.01

• •    下一篇

胃癌中Piwil1基因启动子区rs28416520位点单核苷酸多态性及其临床意义

李珍珍，周兰庭，翟立红，肖 娟，程正江
  

  • 出版日期:2020-10-20 发布日期:2020-10-20

Single nucleotide polymorphism of rs28416520 in Piwil1 gene promoter region is associated with an increased risk of gastric cancer

  • Online:2020-10-20 Published:2020-10-20

RichHTML

76

HTML

PDF

240

摘要： 目的 分析Piwil1基因启动子区域的单核苷酸多态性（SNP）和胃癌的相关性。方法 利用实时定量PCR检测3例胃癌患者肿瘤组织中Piwil1 mRNA的表达，并通过肿瘤转录组测序数据库分析胃癌组织中Piwil1 mRNA的表达水平。采用PCR克隆出Piwil1基因启动子区的序列，直接测序法测定24例胃癌患者和29例健康对照者的基因多态性，并使用SnapGene软件对测序结果进行分析。结果 对Cancer RNA-Seq Nexus数据库查询结果和3例胃癌患者肿瘤组织和癌旁组织的实时定量PCR检测结果进行分析，发现胃癌组织中Piwil1基因表达量较癌旁组织高。检测到Piwil1基因启动子两个CpG区域的7个SNP位点，发现仅有一个SNP位点和胃癌有相关性。CpG 67区域rs28416520位点基因型GG、GA、AA在胃癌组中的频率分别为79.2%、16.7%、4.1%，在健康对照组中分别为37.9%、55.2%、6.9%，胃癌组GG基因型频率显著高于对照组（OR=0.144，95%CI：0.045~0564，χ2=9.071，P<0.01）。胃癌组rs28416520等位基因G的频率显著高于对照组（87.5% vs 65.5%；OR=0.271，95%CI：0.099~0.766, χ2=6.856，P<0.01）。其它6个SNP位点在胃癌组和正常组之间没有显著差异。结论 Piwil1基因启动子 CpG 67区域rs28416520位点基因型GG和等位基因G与胃癌发病风险升高相关，且Piwil1基因在胃癌肿瘤组织中表达升高。

关键词: 胃癌, Piwil1基因, 单核苷酸多态性, CpG

Abstract: Objective To analyze the correlation between the single nucleotide polymorphisms (SNPs) in the promoter of Piwil1 gene and gastric cancer. Methods The expression of Piwil1 mRNA in the tumor tissues of 3 patients with gastric cancer was detected by RT-qPCR, and RNA-Sequencing data from the Cancer RNA-Seq Nexus were analyzed for Piwil1 mRNA expression in gastric patients. Blood samples were collected from 24 gastric cancer patients and 29 healthy control subjects for PCR amplification of Piwil1 gene promoter region. The SNP loci in the promoter region of Piwil1 gene were determined by direct sequencing, and the results were analyzed by SnapGene software. Results Analysis of the data from Cancer RNA-Seq Nexus and the results of RT-qPCR in 3 gastric cancer patients all showed significantly increased Piwil1 expression in gastric cancer tissues compared with the adjacent tissues. Seven SNP loci in two CpG regions of the Piwil1 gene promoter were genotyped, and only one SNP locus was found to be related to gastric cancer. The frequencies of GG, GA, and AA genotypes at the rs28416520 locus in CpG 67 region were 79.2%, 16.7%, and 4.1% in the gastric cancer group, and were 37.9%, 55.2%, and 6.9% in the control group, respectively, showing a significantly higher frequency of the GG genotype in gastric cancer group (OR=0.144, 95%CI: 0.045-0.564, χ2=9.071, P<0.01). The frequency of allele G of the rs28416520 locus was significantly higher in gastric cancer group than in the control group (87.5% vs 65.5%; OR=0.271, 95%CI: 0.099-0.766, χ2=6.856, P<0.01). The genotype or allele frequencies of the other 6 SNPs locus did not differ significantly between gastric cancer group and control group. Conclusions The expression of Piwil1 is increased in gastric cancer tissues as compared with the adjacent tissues. The GG genotype and G allele of rs28416520 within CpG 67 region are associated with an increased risk of gastric cancer.

Key words: gastric cancer, Piwil1 gene, single nucleotide polymorphisms, CpG