本文關鍵詞： 肝癌 PAX8 預后 多態(tài)性 肝癌 預后HBV 變異　出處：《南京醫(yī)科大學》2017年博士論文　論文類型：學位論文

【摘要】：PAX8是蛋白轉錄因子配對盒子家族的成員之一,它編碼在細胞分化和細胞生長過程中發(fā)揮作用的轉錄因子,與肝細胞癌(HCC)的預后有關。通過生物信息學分析,我們確定了作為表達PAX8數(shù)量性狀基因位點(eQTLs)一個新的長鏈非編碼RNA(lncRNA)AC016683.6的幾個單核苷酸多態(tài)性(SNPs)。我們假設lncRNA AC016683.6中的PAX8 eQTLs可能影響肝癌的預后。隨后進一步評估兩個單核苷酸多態(tài)性與非手術治療的331例HBV陽性的HCC患者預后的關系。采用Cox比例風險模型進行生存分析,并校正年齡,性別,吸煙狀況,飲酒狀態(tài),BCLC分期和化療/TACE(經導管肝動脈化療栓塞)等情況。結果:與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等位基因提示較好的預后(rs1110839:調整的HR=0.74,95%CI=0.61-0.91,P=0.004;在相加模型中,rs4848320:調整的HR=0.71,95%CI=0.54-0.94,P=0.015)。此外,在 BCLC-C 期的化療/TACE 患者中,這兩種SNP變異基因型的組合效應更加明顯。我們的研究結果表明lncRNA AC016683.6中的PAX8 eQTLs與中國人群HCC的預后可能存在著關聯(lián)。目的:進一步探討HBV基因型/突變與HCC預后的關聯(lián)。材料和方法:采用前瞻性臨床隨訪研究設計,在331例來自南京醫(yī)科大學附屬第一醫(yī)院及江蘇省腫瘤醫(yī)院經病理組織學或細胞學確診的新發(fā)HCC患者中進行了 HBV基因型/突變檢測,并結合HCC病人的臨床特征和遠期預后信息,分析HBV基因型/突變與HCC預后的關聯(lián)。結果:nt1753(TvsC:調整 HR= 0.73,95%CI = 0.55-0.97,P = 0.035)多態(tài)性改變與HCC患者死亡風險降低相關;在調整年齡、性別、吸煙、飲酒、BCLC分期及放化療情況后,HR = 0.73,95%CI = 0.55-0.97,P = 0.035。結論:是否放化療、年齡、nt1753多態(tài)性改變以及飲酒情況是影響HCC預后的獨立危險因素。
[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.

【學位授予單位】：南京醫(yī)科大學
【學位級別】：博士
【學位授予年份】：2017
【分類號】：R735.7

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