microRNA於血管支架易形成再阻塞患者基因性生物標誌之鑑定

Taipei Medical University Institutional Repository > 藥學院 > 臨床藥物基因體學暨蛋白質體學碩士學位學程 > 博碩士論文 > Item 987654321/61004

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题名:	microRNA於血管支架易形成再阻塞患者基因性生物標誌之鑑定 Investigation of MicroRNA Expression Profiles in the Susceptible Population to In-stent Restenosis
作者:	陳昌蕊 Chen, Chang-Jui
贡献者:	臨床藥物基因體學暨蛋白質體學碩士學位學程吳介信
关键词:	microRNA;支架;再阻塞;基因;生物標誌 MicroRNA;In-stent Restenosis;biomarker
日期:	2016
上传时间:	2021-10-29 16:22:59 (UTC+8)
摘要:	支架內再阻塞（in-stent restenosis；ISR）是目前心導管手術應用的主要缺陷。ISR 是一種反應氣球擴張術合併支架放置後血管損傷的病理現象。約 30%接受氣球擴張術合併裸露支架（bare-metal stent；BMS）放置的病患會發生 ISR。因為目前缺乏專一性的 ISR 臨床生物標記（biomarkers），所以常以效用較佳但價格昂貴許多的藥物釋放支架（drug-eluting stent；DES）來預防性的介入而造成濫用。而DES的使用除了經濟效益的考量，後續與BMS相較併發症嚴重度也仍待商榷。因此，本研究希望找出合適可供臨床上醫師參考的生物標誌，對每個病人是否為易再阻塞體質做評估。microRNAs(miRNAs)是一類長約22個核苷酸的單鏈RNA小分子。lin-4是最早由線蟲發現的miRNA，目前miRNA已在許多生物中被發現，且被廣泛研究於癌症方面的生物標誌。本研究收集臨床再阻塞病人以及無再阻塞病人檢體，以miRNA為標的，分析經由前驅動物實驗以及SNP實驗的生物資訊軟體分析預測，選出合適於restenosis的候選miRNA分子。再將各個miRNA候選分子於兩群病人的高低表現以及共病相關統計分析，目標找出候選miRNA在restenosis的相關機轉，並以此結果，發展出合適的生物標誌模組，供臨床上使用預測病人是否容易再阻塞。 In-stent restenosis (ISR) is a pathological phenomenon in response to vascular injury after balloon angioplasty with stent placement, which occurs in just about 20~30% cases. Because of the lack of ISR specific clinical biomarkers, the drug-eluting stents (DES) were widely abused as preventive interventions at present. Micro-RNAs (miRNAs) are short, noncoding RNA molecules capable of regulating gene expression at post-transcription levels. The functions of miRNAs have provided novel insight into the integrated genetic circuitry remarking cell fate. A growing number of evidences suggested that abnormal expression profiles of miRNAs associated with development of numerous diseases. To date, no reports showed that any miRNA candidates have been used to distinguish the populations with high risk for ISR. Thereby, the purpose of the present study was to identify potential candidates of miRNAs differentially expressed in ISR patients. Five miRNA candidates (mir-142-5p, mir-132-3p, mir-24-2-5p, mir-424-5p and mir-15b-5p) were picked up by the MetaCoreTM software based on experimental data from the proteomics analysis and SNP array. The participants were recruited from the Taipei Medical University Hospital and Taipei Municipal Wanfang Hospital, Taiwan. This human research was approved by TMU-JIRB. 96 participants were recruited and analyzed, each group had nearly half patients which certified by cardiologist. Total miRNA was extracted from blood serum and the expression profiles of the miRNA candidates were analyzed by using SYBR® Green-based real-time PCR. After identification of candidate miRNAs from prediction of bioinformatics, we validated the most potential miRNA biomarkers candidates and seek the function of them in restenosis process by going through literature review. Based on this studies we found that miRNA indeed regulates the core cardiovascular gene network and its functions upstream of pathogenesis pathway. Furthermore, the results of a predication biomarker panel can be developed based on miRNAs we chosed gives a promising strategy for clinical use. Add on the statistics analysis of the results and factors adjustment, it may develop a new scale of biomarker predication in differentiating whether people susceptible in-restenosis process or not. In conclusion, our data mentioned that combining the different miRNAs candidates can provide a promising biomarker panel for therapeutic use for predicting the susceptibility of a patient. Moreover, it can also provide a novel platform for precision medicine and new drug development.
描述:	碩士指導教授：吳介信
数据类型:	thesis
显示于类别:	[臨床藥物基因體學暨蛋白質體學碩士學位學程] 博碩士論文

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