全基因组血清microRNAs表达分析筛选阿尔茨海默病血清生物标志物的研究

发布时间：2018-05-20 08:21

本文选题：阿尔茨海默病 + miRNA　；参考：《青岛大学》2014年硕士论文

【摘要】：背景阿尔茨海默病是最常见的老年性痴呆疾病,其早期诊断是预防和治疗的关键。一种短链(18-24nt)非编码RNA——miRNA,由于其在血清中稳定的存在,且在循环血中的表达谱随着机体生理病理情况的改变而发生变化,从而具有重要应用前景。外周循环血中的微小RNA已作为一类新的生物标记物用于许多神经性疾病。我们推测miRNA在血清中有可能差异表达,从而成为一种新的生物标志物。方法我们采用全基因组筛选的研究策略,运用HiSeq测序技术选取在患者血清内显著表达失调的14种miRNA.进一步应用荧光定量PCR的方法进行小样本复筛和大样本验证,以获得在患者中稳定异常表达的特异性血清微小RNA差异表达谱,通过聚类分析和ROC曲线等评价其临床诊断价值,探讨其临床诊断生物学指标的可行性、特异性及灵敏性。结果与对照组相比,其中6种miRNA(MiR-98-5p, miR-885-5p, miR-483-3p, miR-342-3p, miR-191-5p and miR-let-7d-5p)表达水平显著下降(p0.001),其中miR-342-3p敏感度特异度最高(81.5%/70.1%),其与MMSE水平显著相关。结论本研究证实了6种miRNA可以高灵敏度高特异度的区分阿尔茨海默病人与正常对照老年人。其中miR-342-3p有可能成为潜在的新的无创的阿尔茨海默病早期预警和诊断的生物标记物。
[Abstract]:Background Alzheimer's disease is the most common Alzheimer disease, its early diagnosis is the key to prevention and treatment. A kind of short chain non-coding RNA-miRNA-miRNAs has an important application prospect because of its stable presence in serum, and its expression profile in circulating blood changes with the changes of physiological and pathological conditions of the body. MicroRNA in peripheral circulating blood has been used as a new biomarker for many neurological diseases. We speculate that miRNA may be differentially expressed in serum and thus become a new biomarker. Methods We selected 14 kinds of miRNAs with abnormal expression in patients' serum by HiSeq sequencing with the strategy of whole genome screening. Further, fluorescence quantitative PCR was used to screen small sample and large sample to obtain the differential expression profile of specific serum RNA, which was stable and abnormal in patients. The clinical diagnostic value was evaluated by cluster analysis and ROC curve. To explore the feasibility, specificity and sensitivity of clinical diagnostic biological indexes. Results the expression levels of miR-98-5p, miR-885-5p, miR-483-3p, miR-342-3pand miR-191-5p and miR-let-7d-5pwere significantly decreased in 6 miRNAs compared with the control group. The highest sensitivity of miR-342-3p was 81.5 / 70.1, which was significantly correlated with the level of MMSE. Conclusion this study confirmed that 6 miRNA can distinguish Alzheimer patients from normal controls with high sensitivity and specificity. MiR-342-3p could potentially become a new non-invasive biomarker for early warning and diagnosis of Alzheimer's disease.
【学位授予单位】：青岛大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R749.16

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