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APOB genotypes and CDH13 haplotypes in the cholesterol-related pathway genes predict non-small cell lung cancer survival.

胆固醇相关通路基因中的 APOB 基因型和 CDH13 单倍型预测非小细胞肺癌生存。

  • 影响因子:4.51
  • DOI:10.1158/1055-9965.EPI-19-1262
  • 作者列表:"Wei Q","Deng W","Liu H","Luo S","Clarke J","Glass C","Su L","Lin L","Christiani DC
  • 发表时间:2020-04-01
Abstract

BACKGROUND:Several oncogenic signals are involved in the synthesis, metabolism, transportation and modulation of cholesterol. However, the roles of genetic variants of the cholesterol pathway genes in cancer survival remain unclear. METHODS:We investigated associations between 26,781 common single-nucleotide polymorphisms (SNPs) in 209 genes of the cholesterol pathway and non-small cell lung cancer (NSCLC) survival by utilizing genotyping datasets from two published genome-wide association studies (GWASs). We used multivariate Cox proportional hazards regression and expression quantitative trait loci (eQTL) analyses to identify survival-associated SNPs and their correlations with the corresponding mRNA expression, respectively. We also used Kaplan-Meier survival analysis and bioinformatics functional prediction to further evaluate the identified independent SNPs. RESULTS:We found five independent SNPs (APOB rs1801701C>T; CDH13 rs35859010 C>T, rs1833970 T>A, rs254315 T>C and rs425904 T>C) to be significantly associated with NSCLC survival in both discovery and replication datasets. When the unfavorable genotype (APOB rs1801701CC) and haplotypes (CDH13 rs35859010-rs1833970-rs254315-rs425904 C-A-T-C and T-T-T-T) were combined into a genetic score as the number of unfavorable genotypes/haplotypes (NUGH) in the multivariate analysis, an increased NUGH was associated with a worse survival (Ptrend < 0.0001). In addition, both APOB rs1801701T<C and CDH13 rs425904C<T were correlated with mRNA expression of the genes in normal lung tissues from the genotype-tissue expression (GTEx) project. CONCLUSIONS:Genetic variants of APOB and CDH13 in the cholesterol pathway were associated with NSCLC survival, possibly by affecting their gene expression. IMPACT:Genetic variants of APOB and CDH13 in the cholesterol pathway may provide new scientific insights into NSCLC prognosis.

摘要

背景: 几种致癌信号参与胆固醇的合成、代谢、转运和调节。然而,胆固醇途径基因的遗传变异在癌症生存中的作用仍不清楚。 方法: 我们调查了 26,781 个胆固醇途径基因的 209 个常见单核苷酸多态性 (SNPs) 与非小细胞肺癌 (NSCLC) 的相关性利用两项已发表的全基因组关联研究 (GWASs) 的基因分型数据集生存。我们采用多变量 Cox 比例风险回归和表达数量性状位点 (eQTL) 分析,分别鉴定生存相关 SNPs 及其与相应 mRNA 表达的相关性。我们还使用 Kaplan-Meier 生存分析和生物信息学功能预测来进一步评估已鉴定的独立 SNPs。 结果: 我们发现了 5 个独立的 SNPs (APOB rs1801701C>T; CDH13 rs35859010 C>T,rs1833970 T>A,rs254315 T>C 和 rs425904 T>C) 在发现和复制数据集中与 NSCLC 生存率显著相关。当不利基因型 (APOB rs1801701CC) 和单倍型 (CDH13 rs35859010-rs1833970-rs254315-rs425904 C-A-T-C 和 T-T) 在多变量分析中,结合遗传评分作为不利基因型/单倍型 (NUGH) 的数量,NUGH 增加与较差的生存率相关 (p 趋势 <0.0001)。此外,APOB rs1801701T<C 和 CDH13 rs425904C<T 均与来自基因型-组织表达 (GTEx) 项目的正常肺组织中基因的 mRNA 表达相关。 结论: 胆固醇途径中 APOB 和 CDH13 的遗传变异与 NSCLC 的生存相关,可能通过影响其基因表达。 影响: 胆固醇通路中 APOB 和 CDH13 的遗传变异可能为 NSCLC 预后提供新的科学见解。

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影响因子:1.84
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DOI:10.3892/ol.2019.11149
作者列表:["Das SK","Huang YY","Li B","Yu XX","Xiao RH","Yang HF"]

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