核小体重塑与去乙酰化酶(NuRD)复合体亚基编码基因中的遗传变异与胃癌易感性评估。

Evaluation of genetic variants in nucleosome remodeling and deacetylase (NuRD) complex subunits encoding genes and gastric cancer susceptibility.

作者信息

Zhang Yujuan, Tao Guoquan, Liu Ping, Lu Kai, Han Zhichao, Liu Hanting, Du Mulong, Wang Meilin, Chu Haiyan, Zhang Zhengdong

机构信息

Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China.

Department of Genetic Toxicology, The Key Laboratory of Modern Toxicology of Ministry of Education, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China.

出版信息

Arch Toxicol. 2022 Jun;96(6):1739-1749. doi: 10.1007/s00204-022-03275-5. Epub 2022 Apr 1.

Abstract

Epigenetic complex NuRD (nucleosome remodeling and deacetylase) engages in a range of basic cellular processes, including chromatin modification. Changes in the activity of NuRD complex can influence gastric cancer progression. Multivariate logistic regression analyses were used to estimate the association between single-nucleotide polymorphisms (SNPs) and gastric cancer risk. Expression quantitative trait loci (eQTL) analysis was used to analyze the relationship between the genotypes and gene expression levels using data from the genotype tissue expression project (GTEx). Gene expression was calculated using databases from The Cancer Genome Atlas (TCGA) and The Gene Expression Omnibus (GEO). Kaplan-Meier plotter was used to evaluate the association between gene expression and survival. SNP rs11064275 T allele in CHD4, rs892022 A allele and rs2033481 A allele in GATAD2A were found to contribute to the decreased risk of gastric cancer. The increase in the number of favorable alleles of these three SNPs was associated with a lower risk of gastric cancer. rs2033481 and rs892022 were substantially correlated with GATAD2A mRNA expression levels. Meanwhile, we detected that the CHD4 and GATAD2A mRNA expression was increased in gastric cancer tissues compared with the adjacent normal tissues. Furthermore, we found that patients with higher CHD4 or GATAD2A mRNA expression level had more advantageous overall survival. Our findings indicated that genetic variants in NuRD complex subunits encoding genes may be promising predictors of gastric cancer risk.

摘要

表观遗传复合物NuRD(核小体重塑与去乙酰化酶)参与一系列基本细胞过程,包括染色质修饰。NuRD复合物活性的变化会影响胃癌进展。采用多因素逻辑回归分析来评估单核苷酸多态性(SNP)与胃癌风险之间的关联。利用基因型组织表达计划(GTEx)的数据,通过表达定量性状位点(eQTL)分析来分析基因型与基因表达水平之间的关系。使用来自癌症基因组图谱(TCGA)和基因表达综合数据库(GEO)的数据计算基因表达。使用Kaplan-Meier绘图工具评估基因表达与生存之间的关联。发现CHD4中的SNP rs11064275的T等位基因、GATAD2A中的rs892022的A等位基因和rs2033481的A等位基因有助于降低胃癌风险。这三个SNP的有利等位基因数量增加与较低的胃癌风险相关。rs2033481和rs892022与GATAD2A mRNA表达水平显著相关。同时,我们检测到与相邻正常组织相比,胃癌组织中CHD4和GATAD2A mRNA表达增加。此外,我们发现CHD4或GATAD2A mRNA表达水平较高的患者总体生存更有利。我们的研究结果表明,NuRD复合物亚基编码基因中的遗传变异可能是胃癌风险的有前景的预测指标。

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