肿瘤上皮及其肿瘤交界处间质细胞microRNA的表达和早期大肠癌预后的相关性验证及功能研究

项目名称： 肿瘤上皮及其肿瘤交界处间质细胞microRNA的表达和早期大肠癌预后的相关性验证及功能研究

项目编号： No.81201899

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 肿瘤学2

项目作者： 王漱阳

作者单位： 复旦大学

项目金额： 25万元

中文摘要： 分期相同、不同病例间的大肠癌预后差别很大，用现有技术难以预测。本项目旨在对肿瘤上皮及肿瘤交界处间质细胞microRNA的表达和早期大肠癌预后的相关性进行验证，并研究其功能。我们已通过激光捕获显微切割技术从8例预后不同的大肠癌组织中分离纯净肿瘤上皮及肿瘤交界处间质细胞，并进行microRNA芯片分析，筛选出19个尚未见报道的与早期大肠癌预后相关的microRNA，建立了microRNA功能研究平台。本研究拟通过RT-qPCR验证这19个microRNA在100例早期大肠癌肿瘤上皮及肿瘤交界处间质细胞中的表达；建立并验证可预测早期大肠癌预后的数学模型；共培养原代肿瘤交界处成纤维细胞和大肠癌细胞系，体内外检测候选microRNA对前者细胞表型改变的作用；对后者生物学功能的影响。最终为早期大肠癌预后预测提供新的分子标志物及理论依据，为早期大肠癌的治疗提供潜在靶点。

中文关键词： 早期大肠癌；microRNA；分子标记物；预后；

英文摘要： This study aims to investigate association of microRNA expression in tumor epithelial cells and interface zone stromal cells with prognosis of early colorectal cancer (stage I and II) for identifying new molecular markers of colorectal cancer. In our previous study, we applied laser capture microdissection to isolate both carcinoma epithelial cells and interface zone stromal cells in 8 colorectal surgical tissues from patients (4 died and 4 survival in 5 years) with early stages of colorectal carcinomas. We then performed the microarray analysis and identified the significant association of 19 microRNAs with the prognosis of early stage colorectal carcinomas (fold change > 2 fold and p < 0.05). Those microRNAs are the candidate biomarkers for further validation. In this research proposal, we will perform quantitative RT-PCR to validate the 19 microRNA candidates in an independent cohort of macrodissected FFPE colorectal tissues from 100 patients with stage I and II colorectal carcinomas. We will evaluate the performance of the candidates in the prediction of the tumor metastasis and disease free survival. Furthermore, we will perform the functional study to determine the role of the validated microRNAs on proliferation, apoptosis, evasion and migration effect to the colorectal tumor cells, and on the cell mocelu

英文关键词： early stage colorectal cancer；microRNA；moleculor biomarker；prognosis；