MicroRNA相关基因DROSHA、DICER1、GEMIN4单核苷酸多态性与T细胞淋巴瘤患者预后关系

发布时间：2018-03-16 21:19

本文选题：MicroRNA　切入点：单核苷酸多态性　出处：《第三军医大学》2017年硕士论文　论文类型：学位论文

【摘要】：背景:T细胞淋巴瘤(T-cell lymphoma,TCL)是起源成熟或者胸腺后T淋巴细胞以及自然杀伤(NK)细胞的淋巴造血系统肿瘤,异质性高,大部分T细胞淋巴瘤恶性程度较B细胞淋巴瘤高,预后差。我国TCL发病率显著高于西方,大概占淋巴瘤的25%。国内外,临床上各种类型淋巴瘤在国际预后指数(international prognostic index,IPI)的基础上,结合各自的特点、综合其他预后因素形成各自不同的IPI,以此评价患者的预后,但此评分标准尚不能完全确切的评判所有TCL患者的预后情况。小RNA(Micro RNA,miRNA)是一类由大约21-24个核苷酸组成、高度保守的、内源性非编码小RNA,参与基因转录后调控。现已有文献报道mi RNA与癌症的发生、发展相关。在人类基因组的遗传变异中,单核苷酸多态性(Single nucleotide polymorphism,SNP)是最常见的一种形式,而miRNA相关基因的多态性与mi RNA的合成、下游生物学作用的发挥有关。目前有关mi RNA相关基因多态性与TCL患者预后关联的报道很少。目的:探讨microRNA相关基因DROSHA rs10719和rs6877842、DICER1 rs3742330和GEMIN4 rs3744741单核苷酸多态性与T细胞淋巴瘤患者预后的关系。材料和方法:运用聚合酶链式反应-限制性片段长度多态(PCR-RFLP)技术,对本研究共收集的163个TCL患者外周血标本进行分析,先后检测4个SNP的基因型,最后综合临床相关数据探讨这4个SNP与患者完全缓解(complete remission,CR)率和总体生存(overall survival,OS)率的相关性。结果:临床特征与TCL患者CR率和OS率的相关性分析结果显示:病理类型、肿瘤分期、血清乳酸脱氢酶(lactate dehydrogenase,LDH)水平及IPI评分与CR率和OS率显著相关。Logistic-Regression分析结果显示rs6877842和rs3742330是TCL患者CR率有关的独立预后因素。在rs6877842的CG、CC两种基因型中,携带CG基因型的患者CR率明显优于携带CC基因型的。在rs3742330的GG、GA、AA三种基因型中,携带GG基因型的患者CR率显著优于携带GA基因型或AA基因型的患者。多因素Cox模型分析结果显示rs3742330是与TCL患者OS有关联的独立预后因素,其中携带GG基因型的患者OS率明显高于携带GA基因型或AA基因型的患者。而rs10719和rs3744741与CR率或OS率均无明显相关性。结论:DROSHA rs6877842和DICER1 rs3742330是TCL患者CR率相关的独立预后因素;DICER1 rs3742330也是TCL患者OS率相关的独立预后因素。有利于预测TCL患者的缓解率和生存时间。
[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.
【学位授予单位】：第三军医大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R733.1

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