权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Mitochondria proteome of ulcerative colitis associated dysplasia

溃疡性结肠炎相关发育不良的线粒体蛋白质组

基本信息

批准号：
8510603
负责人：
Ru Chen
金额：
$ 16.08万
依托单位：
UNIVERSITY OF WASHINGTON
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-07-13 至 2016-06-30
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): Patients with extensive ulcerative colitis (UC) have a substantially increased risk of colon cancer. The current screening recommendations, which require frequent colonoscopic surveillance of these patients, are expensive, time consuming, and invasive. An objective biomarker of dysplasia would have great clinical value in the management of cancer risk in UC patients. UC-associated cancer progresses from dysplasia to cancer and is associated with mitochondrial dysfunction, which has long been associated with degenerative diseases, cancer, and aging. Our recent proteomics studies reveal that mitochondrial proteins are involved in UC neoplastic progression and could be valuable targets for biomarker development. The objectives of this research are to better understand the role of mitochondrial proteins underlying the neoplastic progression in chronic UC; and further, to employ this knowledge for improved, more cost effective surveillance-to differentiate the subset of UC patients who need colonoscopy from those who do not. In the proposed study, cutting-edge quantitative proteomics and bioinformatics technologies will be applied to discover aberrant mitochondrial proteins that are associated with precursor lesions during UC neoplastic progression (Aim 1). The identified aberrant mitochondrial proteins will be complementarily characterized using immunochemistry (Aim 2) and targeted proteomics (Aim 3). This project may lead to the discovery of protein biomarkers with direct clinical utility in decision-making for colonoscopy and thus could potentially reduce the cost and patient discomfort associated with colonoscopy. Moreover, the proposed comprehensive analysis of mitochondrial proteome will improve the understanding of the mitochondrial proteome in cancer progression, an area for which we currently have very limited information. The study described is based on our unique resource of material obtained from ulcerative colitis patients and the close-knit collaboration of investigators who have been working together for more than ten years. Successful completion of this proposal will lead to: 1) better understanding of alterations in mitochondrial proteome in UC associated dysplasia and cancer; 2) identification of biomarker candidates to predict UC dysplasia, providing a less invasive, cost effective method to assist UC cancer surveillance.

描述(由申请人提供)：广泛性溃疡性结肠炎(UC)患者患结肠癌的风险显著增加。目前的筛查建议需要对这些患者进行频繁的结肠镜检查，费用昂贵，耗时长，而且具有侵入性。作为非典型增生的客观生物标记物，在UC患者的癌症风险管理中具有重要的临床价值。UC相关癌症从不典型增生进展到癌症，并与线粒体功能障碍有关，线粒体功能障碍长期以来一直与退行性疾病、癌症和衰老有关。我们最近的蛋白质组学研究表明，线粒体蛋白参与了UC的肿瘤进展，并可能成为开发生物标记物的有价值的靶点。这项研究的目的是更好地了解线粒体蛋白在慢性UC肿瘤进展中的作用；进一步，利用这一知识进行改进的、更具成本效益的监测-区分需要结肠镜检查的UC患者和不需要结肠镜检查的UC患者。在这项拟议的研究中，尖端的定量蛋白质组学和生物信息学技术将被应用于发现与UC肿瘤进展过程中的前驱病变相关的异常线粒体蛋白(目标1)。识别的异常线粒体蛋白将利用免疫化学(AIM 2)和靶向蛋白质组学(AIM 3)进行互补鉴定。该项目可能导致发现具有直接临床实用价值的蛋白质生物标记物结肠镜检查，因此可能会降低与结肠镜检查相关的成本和患者的不适。此外，拟议的线粒体蛋白质组综合分析将提高对线粒体蛋白质组在癌症进展中的理解，目前我们对这一领域的信息非常有限。所描述的这项研究是基于我们从溃疡性结肠炎患者获得的独特材料来源，以及合作了十多年的研究人员的密切合作。这项建议的成功完成将导致：1)更好地了解UC相关异型增生和癌症中线粒体蛋白质组的变化；2)识别预测UC异型增生的候选生物标记物，提供一种侵入性更小、成本效益更高的方法来辅助UC癌症监测。