Prognostic Significance of Tag SNP rs1045411 in HMGB1 of the Aggressive Gastric Cancer in a Chinese Population.
Prognostic Significance of Tag SNP rs1045411 in HMGB1 of the Aggressive Gastric Cancer in a Chinese Population.
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HMGB1 标签 SNP rs1045411 对中国人群侵袭性胃癌的预后意义
DOI：
10.1371/journal.pone.0154378
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
He X
中科院分区：
文献类型：
--
作者：
Bao G;Qu F;He L;Zhao H;Wang N;Ji G;He X
令人信服的证据表明，高迁移率族蛋白 1 (HMGB1) 基因在癌症的发生和进展中发挥着至关重要的作用。本研究旨在评估HMGB1基因中的单核苷酸多态性（SNP）对胃癌（GC）患者生存的影响。选择来自 HMGB1 基因的三个标签 SNP，并使用 Sequenom iPEX 基因分型系统在 1030 名 GC 患者队列中进行基因分型（训练组 704 名，验证组 326 名）。采用多变量Cox比例风险模型和Kaplan-Meier曲线进行预后分析。与 GG 基因型相比，HMGB1 基因中 SNP rs1045411 的 AG/AA 基因型与 704 名 GC 患者中较好的总生存期 (OS) 显着相关（HR = 0.77，95% CI：0.60-0.97，P = 0.032）。这种预后效应在独立验证集和汇总分析中得到了验证（HR = 0.80，95% CI：0.62-0.99，P = 0.046；HR = 0.78，95% CI：0.55-0.98，P = 0.043）。分层分析显示，与有利阶层患者相比，rs1045411 AG/AA基因型对不良阶层患者的保护作用更为突出。此外，rs1045411 基因型和 Lauren 分类、分化、分期或辅助化疗之间对 GC 患者的 OS 具有很强的联合预测作用。此外，功能测定表明 rs1045411 对 HMGB1 表达有显着影响。我们的结果表明，HMGB1 中的 rs1045411 与中国胃癌患者术后的临床结果显着相关，尤其是那些处于侵袭状态的患者，这值得在其他种族人群中进一步验证。
Compelling evidences have suggested that high mobility group box-1 (HMGB1) gene plays a crucial role in cancer development and progression. This study aimed to evaluate the effects of single nucleotide polymorphisms (SNPs) in HMGB1 gene on the survival of gastric cancer (GC) patients. Three tag SNPs from HMGB1 gene were selected and genotyped using Sequenom iPEX genotyping system in a cohort of 1030 GC patients (704 in training set, 326 in validation set). Multivariate Cox proportional hazard model and Kaplan-Meier Curve were used for prognosis analysis. AG/AA genotypes of SNP rs1045411 in HMGB1 gene were significantly associated with better overall survival (OS) in a set of 704 GC patients when compared with GG genotypes (HR = 0.77, 95% CI: 0.60–0.97, P = 0.032). This prognostic effect was verified in an independent validation set and pooled analysis (HR = 0.80, 95% CI: 0.62–0.99, P = 0.046; HR = 0.78, 95% CI: 0.55–0.98, P = 0.043, respectively). In stratified analysis, the protective effect of rs1045411 AG/AA genotypes was more prominent in patients with adverse strata, compared with patients with favorable strata. Furthermore, strong joint predictive effects on OS of GC patients were noted between rs1045411 genotypes and Lauren classification, differentiation, stage or adjuvant chemotherapy. Additionally, functional assay indicated a significant effect of rs1045411 on HMGB1 expression. Our results suggest that rs1045411 in HMGB1 is significantly associated with clinical outcomes of Chinese GC patients after surgery, especially in those with aggressive status, which warrants further validation in other ethnic populations.