PAX8数量性状位点及HBV变异与肝癌预后的关系研究
本文关键词: 肝癌 PAX8 预后 多态性 肝癌 预后HBV 变异 出处:《南京医科大学》2017年博士论文 论文类型:学位论文
【摘要】:PAX8是蛋白转录因子配对盒子家族的成员之一,它编码在细胞分化和细胞生长过程中发挥作用的转录因子,与肝细胞癌(HCC)的预后有关。通过生物信息学分析,我们确定了作为表达PAX8数量性状基因位点(eQTLs)一个新的长链非编码RNA(lncRNA)AC016683.6的几个单核苷酸多态性(SNPs)。我们假设lncRNA AC016683.6中的PAX8 eQTLs可能影响肝癌的预后。随后进一步评估两个单核苷酸多态性与非手术治疗的331例HBV阳性的HCC患者预后的关系。采用Cox比例风险模型进行生存分析,并校正年龄,性别,吸烟状况,饮酒状态,BCLC分期和化疗/TACE(经导管肝动脉化疗栓塞)等情况。结果:与rs1110839的T等位基因和rs4848320的C等位基因相比,rs1110839的G等位基因和rs4848320的T等位基因提示较好的预后(rs1110839:调整的HR=0.74,95%CI=0.61-0.91,P=0.004;在相加模型中,rs4848320:调整的HR=0.71,95%CI=0.54-0.94,P=0.015)。此外,在 BCLC-C 期的化疗/TACE 患者中,这两种SNP变异基因型的组合效应更加明显。我们的研究结果表明lncRNA AC016683.6中的PAX8 eQTLs与中国人群HCC的预后可能存在着关联。目的:进一步探讨HBV基因型/突变与HCC预后的关联。材料和方法:采用前瞻性临床随访研究设计,在331例来自南京医科大学附属第一医院及江苏省肿瘤医院经病理组织学或细胞学确诊的新发HCC患者中进行了 HBV基因型/突变检测,并结合HCC病人的临床特征和远期预后信息,分析HBV基因型/突变与HCC预后的关联。结果:nt1753(TvsC:调整 HR= 0.73,95%CI = 0.55-0.97,P = 0.035)多态性改变与HCC患者死亡风险降低相关;在调整年龄、性别、吸烟、饮酒、BCLC分期及放化疗情况后,HR = 0.73,95%CI = 0.55-0.97,P = 0.035。结论:是否放化疗、年龄、nt1753多态性改变以及饮酒情况是影响HCC预后的独立危险因素。
[Abstract]:PAX8 is a member of the paired box transcription factor family, transcription factor of its encoding growth in cell differentiation and cell process, and hepatocellular carcinoma (HCC) prognosis. Through bioinformatics analysis, we determined the expression of PAX8 as a quantitative trait loci for base (eQTLs) a long chain of new the non RNA (lncRNA) encoding several AC016683.6 single nucleotide polymorphism (SNPs). We assume that the lncRNA AC016683.6 PAX8 eQTLs may influence the prognosis of hepatocellular carcinoma. Then further evaluate the relationship between treatment of two single nucleotide polymorphisms and non operation of 331 cases of HBV positive HCC patients. Cox proportional hazards model was used for survival analysis. And adjustment for age, gender, smoking status, drinking status, staging and /TACE BCLC chemotherapy (transcatheter arterial chemoembolization) etc. RESULTS: the rs1110839 and T allele and rs4848320 allele C Compared with the rs1110839 gene, the G allele and rs4848320 allele of T indicates a good prognosis (rs1110839: HR=0.74,95%CI=0.61-0.91, P=0.004; in the additive model, rs4848320: adjusted HR=0.71,95%CI=0.54-0.94, P=0.015). In addition, in stage BCLC-C / TACE chemotherapy in patients with combined effect of these two kinds of SNP genotype were more obvious. Our results suggest that the prognosis of lncRNA AC016683.6 in PAX8 eQTLs and HCC Chinese populations may exist. Objective: to further investigate the genotype HBV / HCC mutation associated with prognosis. Materials and methods: the prospective study design and clinical follow-up, in 331 cases from the First Affiliated Hospital of Nanjing Medical University and the tumor hospital of Jiangsu province by histology or cytology newly diagnosed HCC patients were detected HBV gene mutation / type, and combined with clinical features and long-term HCC patients Prognostic information, analysis of genotype HBV / HCC mutation associated with prognosis. Results: nt1753 (TvsC: HR= 0.73,95%CI = 0.55-0.97, P = 0.035) polymorphisms and HCC in patients with lower risk of death; after adjusting for age, sex, smoking, drinking, BCLC staging and the chemotherapy after HR = 0.73,95%CI = 0.55-0.97 P = 0.035., conclusion: whether chemotherapy, age, nt1753 polymorphism change and drinking is an independent risk factor of the prognosis of HCC.
【学位授予单位】:南京医科大学
【学位级别】:博士
【学位授予年份】:2017
【分类号】:R735.7
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