Molecular Differences Predicting Tumor Progression in Colorectal Cancer (PQ #14)

预测结直肠癌肿瘤进展的分子差异（PQ

基本信息

批准号：
8538333
负责人：
Richard Brott Halberg
金额：
$ 15.38万
依托单位：
UNIVERSITY OF WISCONSIN-MADISON
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：
2012-09-01 至 2014-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8538333
关键词：
Address Adenocarcinoma Advanced Malignant Neoplasm Animal Model Animals Attention Behavior Benign Biological Markers Biopsy Cancer Etiology Cancerous Characteristics Chemoprevention Clinical Colon Colonoscopy Colorectal Colorectal Cancer Colorectal Neoplasms Controlled Environment DNA Microarray Chip Disease Progression Eligibility Determination Event Gene Expression Genes Genetic Gold Gray unit of radiation dose Heterogeneity Human Image Imaging Techniques Individual Lead Lesion Life Malignant - descriptor Malignant Lymph Node Neoplasm Malignant Neoplasms Modeling Molecular Molecular Analysis Molecular Profiling Monitor Mus Mutation Natural History Neoplasm Metastasis Neoplasms Outcome Patients Polypectomy Population Precancerous Polyp Prevention Prevention strategy Procedures Protocols documentation Recommendation Risk Schedule Staging Stratification Testing Time Tissue Sample United States adenoma arm base cost design high risk improved interest malignant state mortality mouse model novel novel strategies prognostic prospective research study screening tumor tumor progression virtual

项目摘要

DESCRIPTION (provided by applicant): Colorectal tumors have different fates. Kim and colleagues demonstrated that early adenomas in humans could grow, remain static, or even spontaneously regress as determined by longitudinally monitoring via virtual colonography (N Engl J Med. 357(14):1403-12, 2007). We found that early adenomas in the mouse had the same fates (Acad Radiol. 16(12):1475-82, 2009). Moreover, a significant percentage of adenomas eventually progress to invasive adenocarcinomas that occasionally metastasize to regional lymph nodes (Cancer Res. 69(14):5768-75, 2009). The progression of tumors from a benign to malignant state can now be meticulously detailed because of recent advances in micro-imaging. We plan to monitor tumors as they progress, collecting biopsies for histopathological assessment and molecular analysis (Aim 1). Transcriptional changes associated with progression can then be elucidated with DNA microarrays. The profile of adenomas that progress to invasive adenocarcinomas will be compared to the profile of adenomas that do not progress (Aim 2). This type of experiment is not feasible in humans because the clinical outcome of any tumor is unknowable. Identifying predictive biomarkers in a mouse model is an important first step towards identifying genes of interest in humans. Our current understanding of the genetic events leading to human colorectal cancer (CRC) is not sufficiently detailed to allow us to provide sophisticated prognostic information to patients based on the molecular characteristics of their tumors. More detailed information would lead to personalized risk stratification and screening recommendations for patients based on genetic changes present within their tumors. This approach would minimize the risks garnered by unnecessary screening tests, while maximizing the chances that high-risk patients undergo more appropriately timed surveillance. It could also guide novel strategies for chemoprevention and treatment of CRC.

描述（由申请人提供）：结直肠肿瘤的命运不同。 Kim及其同事表明，人类的早期腺瘤可以通过通过虚拟造影术纵向监测来确定，可以保持静态，甚至自发回归（N Engl JMed。357（14）：1403-12，2007）。我们发现，小鼠中的早期腺瘤具有相同的命运（AcadRadiol。16（12）：1475-82，2009）。此外，很大一部分腺瘤最终会发展为侵入性腺癌，这些腺癌偶尔会转移到区域淋巴结（CancerRes。69（14）：5768-75，2009）。现在，由于微影像的最新进展，肿瘤从良性到恶性状态的进展现在可以详细介绍。我们计划随着肿瘤的进行监测，收集活检以进行组织病理学评估和分子分析（AIM 1）。然后可以用DNA微阵列阐明与进展相关的转录变化。将发展为侵入性腺癌的腺瘤的特征将与不进行的腺瘤的特征进行比较（AIM 2）。这种类型的实验在人类中是不可行的，因为任何肿瘤的临床结果都是不可知的。在小鼠模型中识别预测性生物标志物是识别人类感兴趣基因的重要第一步。我们目前对导致人类结肠癌（CRC）的遗传事件的理解不足以使我们能够为基于患者的复杂预后信息提供复杂的预后信息关于其肿瘤的分子特征。更详细的信息将根据其肿瘤中存在的遗传变化为患者提供个性化的风险分层和筛查建议。这种方法将最大程度地减少不必要的筛查测试所获得的风险，同时最大程度地增加了高危患者进行更适当定时监视的机会。它还可以指导CRC化学预防和治疗的新型策略。