Zhu Xiao, Kong Qingming, Xie Liwei, Chen Zhihong, Li Hongmei, Zhu Zhu, Huang Yongmei, Lan Feifei, Luo Haiqing, Zhan Jingting, Ding Hongrong, Lei Jinli, Xiao Qin, Fu Weiming, Fan Wenguo, Zhang Jinfang, Luo Hui
Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, Dongguan Scientific Research Center, Guangdong Medical University, Dongguan, China.
Cancer Center, Medical College of Georgia, Georgia Health Sciences University, Augusta, GA, USA.
Oncotarget. 2017 Dec 26;9(17):13222-13230. doi: 10.18632/oncotarget.23812. eCollection 2018 Mar 2.
Previous studies showed that the low expressions of chromodomain-helicase-DNA-binding protein 5 (CHD5) were intensively associated with deteriorative biologic and clinical characteristics as well as outcomes in many tumors. The aim of this study is to determine whether single nucleotide polymorphisms (SNPs) contribute to the prognosis of hepatocellular carcima (HCC). The SNPs were selected according to their linkage disequilibrium (LD) in the targeted next-generation sequencing (NGS) and then genotyped with TaqMan probers. We revealed a rare haplotype AG in (SNPs: rs12564469-rs9434711) was markedly associated with HCC prognosis. The univariate and multivariate regression analyses revealed the patients with worse overall survival time were those with tumor metastasis and haplotype AG, as well as cirrhosis, poor differentiation and IV-TNM stage. Based on the available public databases, we discovered the significant association between haplotype AG and mRNA expressions only existed in Chinese. These data proposed that the potentially genetic haplotype might functionally contribute to HCC prognosis and mRNA expressions.
先前的研究表明,染色体结构域解旋酶DNA结合蛋白5(CHD5)的低表达与许多肿瘤的生物学和临床特征恶化以及预后密切相关。本研究的目的是确定单核苷酸多态性(SNP)是否对肝细胞癌(HCC)的预后有影响。根据目标下一代测序(NGS)中的连锁不平衡(LD)选择SNP,然后用TaqMan探针进行基因分型。我们发现(SNP:rs12564469-rs9434711)中一种罕见的单倍型AG与HCC预后显著相关。单变量和多变量回归分析显示,总生存时间较差的患者是那些有肿瘤转移和单倍型AG,以及有肝硬化、低分化和IV期TNM分期的患者。基于现有的公共数据库,我们发现单倍型AG与mRNA表达之间的显著关联仅在中国人群中存在。这些数据表明,潜在的遗传单倍型可能在功能上影响HCC的预后和mRNA表达。