本文選題：MicroRNA　切入點：單核苷酸多態(tài)性　出處：《第三軍醫(yī)大學》2017年碩士論文　論文類型：學位論文

【摘要】：背景:T細胞淋巴瘤(T-cell lymphoma,TCL)是起源成熟或者胸腺后T淋巴細胞以及自然殺傷(NK)細胞的淋巴造血系統(tǒng)腫瘤,異質性高,大部分T細胞淋巴瘤惡性程度較B細胞淋巴瘤高,預后差。我國TCL發(fā)病率顯著高于西方,大概占淋巴瘤的25%。國內(nèi)外,臨床上各種類型淋巴瘤在國際預后指數(shù)(international prognostic index,IPI)的基礎上,結合各自的特點、綜合其他預后因素形成各自不同的IPI,以此評價患者的預后,但此評分標準尚不能完全確切的評判所有TCL患者的預后情況。小RNA(Micro RNA,miRNA)是一類由大約21-24個核苷酸組成、高度保守的、內(nèi)源性非編碼小RNA,參與基因轉錄后調(diào)控�，F(xiàn)已有文獻報道m(xù)i RNA與癌癥的發(fā)生、發(fā)展相關。在人類基因組的遺傳變異中,單核苷酸多態(tài)性(Single nucleotide polymorphism,SNP)是最常見的一種形式,而miRNA相關基因的多態(tài)性與mi RNA的合成、下游生物學作用的發(fā)揮有關。目前有關mi RNA相關基因多態(tài)性與TCL患者預后關聯(lián)的報道很少。目的:探討microRNA相關基因DROSHA rs10719和rs6877842、DICER1 rs3742330和GEMIN4 rs3744741單核苷酸多態(tài)性與T細胞淋巴瘤患者預后的關系。材料和方法:運用聚合酶鏈式反應-限制性片段長度多態(tài)(PCR-RFLP)技術,對本研究共收集的163個TCL患者外周血標本進行分析,先后檢測4個SNP的基因型,最后綜合臨床相關數(shù)據(jù)探討這4個SNP與患者完全緩解(complete remission,CR)率和總體生存(overall survival,OS)率的相關性。結果:臨床特征與TCL患者CR率和OS率的相關性分析結果顯示:病理類型、腫瘤分期、血清乳酸脫氫酶(lactate dehydrogenase,LDH)水平及IPI評分與CR率和OS率顯著相關。Logistic-Regression分析結果顯示rs6877842和rs3742330是TCL患者CR率有關的獨立預后因素。在rs6877842的CG、CC兩種基因型中,攜帶CG基因型的患者CR率明顯優(yōu)于攜帶CC基因型的。在rs3742330的GG、GA、AA三種基因型中,攜帶GG基因型的患者CR率顯著優(yōu)于攜帶GA基因型或AA基因型的患者。多因素Cox模型分析結果顯示rs3742330是與TCL患者OS有關聯(lián)的獨立預后因素,其中攜帶GG基因型的患者OS率明顯高于攜帶GA基因型或AA基因型的患者。而rs10719和rs3744741與CR率或OS率均無明顯相關性。結論:DROSHA rs6877842和DICER1 rs3742330是TCL患者CR率相關的獨立預后因素;DICER1 rs3742330也是TCL患者OS率相關的獨立預后因素。有利于預測TCL患者的緩解率和生存時間。
[Abstract]:Background: the T-cell lymphomatosis (TCLs) is a tumor of lymphatic hematopoietic system of mature or retrothymic T lymphocytes and natural killer NKK cells with high heterogeneity. Most T-cell lymphomas are more malignant than B-cell lymphomas. The prognosis is poor. The incidence of TCL in China is significantly higher than that in the West, accounting for about 25% of the lymphoma. At home and abroad, various types of lymphoma are based on the international prognostic index and their respective characteristics. Other prognostic factors are taken into account to evaluate the prognosis of patients with TCL. However, this score does not exactly determine the prognosis of all patients with TCL. Small RNAs miRNAs are composed of about 21-24 nucleotides and are highly conserved. Endogenous non-coding small RNAs are involved in gene posttranscriptional regulation. It has been reported that mi RNA is associated with the occurrence and development of cancer. In the genetic variation of the human genome, single nucleotide polymorphismNPs are the most common form. The polymorphism of miRNA related gene and the synthesis of miRNA, There are few reports about the association between the polymorphism of mi RNA associated gene and prognosis of TCL patients. Objective: to investigate the single nucleotide polymorphisms of DROSHA rs10719 and rs6877842 DICER1 rs3742330 and GEMIN4 rs3744741 in patients with TCL. Materials and methods: polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique was used. The peripheral blood samples collected from 163 patients with TCL were analyzed and 4 genotypes of SNP were detected. Finally, the correlation between the four SNP and the complete remission rate of complete remission and the overall survival rate of patients with TCL was discussed. Results: the correlation analysis between clinical features and CR rate and OS rate of TCL patients showed that: pathological type, tumor stage, tumor stage. Serum lactate dehydrogenase level and IPI score were significantly correlated with CR rate and OS rate. The results showed that rs6877842 and rs3742330 were independent prognostic factors related to CR rate in TCL patients. The CR rate of patients with CG genotype was significantly higher than that with CC genotype. The CR rate of patients with GG genotype was significantly higher than that of patients with GA genotype or AA genotype. Multivariate Cox model analysis showed that rs3742330 was an independent prognostic factor associated with OS in TCL patients. The OS rate of patients with GG genotype was significantly higher than that of patients with GA genotype or AA genotype, while rs10719 and rs3744741 had no significant correlation with CR rate or OS rate. Conclusion\\\%\\%\%\% drop\%\%\%\%\%\%\%\%\%. DICER1 rs3742330 is also an independent prognostic factor related to OS rate in TCL patients, which is helpful to predict remission rate and survival time of TCL patients.
【學位授予單位】：第三軍醫(yī)大學
【學位級別】：碩士
【學位授予年份】：2017
【分類號】：R733.1

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