本文關(guān)鍵詞： 肝癌 PAX8 預(yù)后 多態(tài)性 肝癌 預(yù)后HBV 變異　出處：《南京醫(yī)科大學(xué)》2017年博士論文　論文類(lèi)型：學(xué)位論文

【摘要】：PAX8是蛋白轉(zhuǎn)錄因子配對(duì)盒子家族的成員之一,它編碼在細(xì)胞分化和細(xì)胞生長(zhǎng)過(guò)程中發(fā)揮作用的轉(zhuǎn)錄因子,與肝細(xì)胞癌(HCC)的預(yù)后有關(guān)。通過(guò)生物信息學(xué)分析,我們確定了作為表達(dá)PAX8數(shù)量性狀基因位點(diǎn)(eQTLs)一個(gè)新的長(zhǎng)鏈非編碼RNA(lncRNA)AC016683.6的幾個(gè)單核苷酸多態(tài)性(SNPs)。我們假設(shè)lncRNA AC016683.6中的PAX8 eQTLs可能影響肝癌的預(yù)后。隨后進(jìn)一步評(píng)估兩個(gè)單核苷酸多態(tài)性與非手術(shù)治療的331例HBV陽(yáng)性的HCC患者預(yù)后的關(guān)系。采用Cox比例風(fēng)險(xiǎn)模型進(jìn)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(jīng)導(dǎo)管肝動(dòng)脈化療栓塞)等情況。結(jié)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(yù)后(rs1110839:調(diào)整的HR=0.74,95%CI=0.61-0.91,P=0.004;在相加模型中,rs4848320:調(diào)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(yīng)更加明顯。我們的研究結(jié)果表明lncRNA AC016683.6中的PAX8 eQTLs與中國(guó)人群HCC的預(yù)后可能存在著關(guān)聯(lián)。目的:進(jìn)一步探討HBV基因型/突變與HCC預(yù)后的關(guān)聯(lián)。材料和方法:采用前瞻性臨床隨訪研究設(shè)計(jì),在331例來(lái)自南京醫(yī)科大學(xué)附屬第一醫(yī)院及江蘇省腫瘤醫(yī)院經(jīng)病理組織學(xué)或細(xì)胞學(xué)確診的新發(fā)HCC患者中進(jìn)行了 HBV基因型/突變檢測(cè),并結(jié)合HCC病人的臨床特征和遠(yuǎn)期預(yù)后信息,分析HBV基因型/突變與HCC預(yù)后的關(guān)聯(lián)。結(jié)果:nt1753(TvsC:調(diào)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(fēng)險(xiǎn)降低相關(guān);在調(diào)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(jié)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(yù)后的獨(dú)立危險(xiǎn)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(xué)位授予單位】：南京醫(yī)科大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2017
【分類(lèi)號(hào)】：R735.7

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本文編號(hào)：1519663