| Summary: | 碩士 === 國立陽明大學 === 醫學生物技術暨檢驗學系暨研究所 === 99 === Abstract
Colorectal cancer (CRC) is a leading cause of cancer death in the world. In 2008, there are over 1.2 million new CRC cases and 608,700 related deaths worldwide. In recent years, the numbers of CRC incidence have increased considerably in some area including Eastern Asia. However, to date, there is no non-invasive biomarker that can be used to detect CRC at early stage and to monitor the progression of CRC. It is beneficial to develop a new biomarker for CRC. MicroRNAs are non-coding, small (18~22 nt in size) regulatory RNAs that are deregulated in many human diseases including cancer. Recently, microRNAs can be detected in body fluids and their fluctuant expression patterns have relations with certain disease status including cancers.
In this study, my objective is to evaluate circulating microRNA as a potential novel biomarker of CRC. I am interrogating the expression level of circulating microRNAs as well as corresponding CRC tissues. Initially, I established the standard experimental conditions to prepare total RNAs from small volume of serum and then employed stem-loop RT-PCR for microRNAs identification. My data demonstrated that circulating microRNAs are fairly stable and their expression levels are reproducibly consistent among individuals. Subsequently, I screened over 34 microRNAs using CRC cancer tissues and identified 13 microRNAs could be deregulated. Among them, miR-92a, miR-221, miR-18a, miR-584, miR-17, miR-21, miR-20a, miR-31, miR-135, miR-96 are up-regulated and miR-1, miR-9, miR-133a are down-regulated. We further analysis these deregulated microRNAs in the serums of these patients. We found that while the most of microRNAs are readily found in CRC tissues, only a few numbers of microRNAs could be observed in matching serum samples. These microRNAs observed in serums are strongly correlated in tissues sample. There is a significant clinical association that the expression level of circulating miR-92a, miR-221, miR-21 with tumor stages and tumor sizes. The expression level of circulating miR-221 have changed in CRC patients before and after surgical removal of the tumor.
In conclusion, results from this study suggest that circulating miR-92a, miR-221, and miR-21 might have the potential to serve as novel blood-based biomarker for CRC prediction.
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