Simplified Diagnosis of a Prognostic Wound Response Signature in Breast Cancer

乳腺癌预后伤口反应特征的简化诊断

基本信息

批准号：
7179669
负责人：
Howard Y Chang
金额：
$ 15.8万
依托单位：
STANFORD UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-07-01 至 2009-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7179669
关键词：
Academic Medical Centers Algorithms Archives Bioinformatics Biological Markers Blood Vessels Cancer Etiology Cancer Patient Cells Cessation of life Clinical DNA amplification Daily Data Detection Diagnosis Ensure Epithelial Fibroblasts Formalin Funding Gene Expression Profiling Genes Genomics Goals Growth Healed Human Human body Malignant Neoplasms Measures Messenger RNA Methods Microarray Analysis Modeling Molecular Natural regeneration Neoplasm Metastasis Numbers Outcome Paraffin Embedding Pathologic Patients Physiological Polymerase Chain Reaction Process RNA amplification Recruitment Activity Regulator Genes Risk Assessment Risk Factors Sampling Serum Site Specimen Standards of Weights and Measures Technology Testing Tissue Microarray Tissues Transcript Tumor Tissue United States Woman Wound Healing base healing improved malignant breast neoplasm novel prognostic response tool tumor tumor progression wound

项目摘要

DESCRIPTION (provided by applicant): The human body has a tremendous capacity for healing, but the ability of cells to grow, regenerate tissues, and recruit new blood vessels may also be misused during cancer progression. In many common cancers, especially breast cancer, the ability of tumors to express a set of 512 genes seen normally in a model of wound response is a powerful and accurate predictor of subsequent metastasis and death. The prognostic information of the 512 gene "wound signature" was independent of and more informative than traditional clinical and pathologic risk factors. The wound signature was also independent of previously identified prognostic signatures and molecular markers. However, the large number of genes involved renders the wound signature difficult to implement in daily clinical practice. The central goal of this proposal is to develop technologies that will greatly simplify the diagnosis of the wound signature. We propose to develop two technologies toward this end. First, we will develop a method to diagnose the wound signature based on detecting DNA amplification of its two regulator genes. Our recent discovery that the wound signature is a consequence of amplification of two key growth regulator genes predicts that measuring the regulator genes will be sufficient to diagnose the wound signature and to prognosticate patient outcome. Second, we will develop a novel gene picking algorithm and RNA amplification technology that can reproduce the prognostic power of the wound signature by measuring only a small fraction of gene transcripts from tumor samples. At the end of the funding period, we envision the capacity to diagnose the wound signature from standard formalin-fixed, paraffin embedded tumor sections. Breast cancer is the second most common cause of cancer death for women in the United States. These deaths are most often caused by the spread of breast cancer to other sites of the body, a process that involves genes normally reserved for wound healing. Improved technology to identify the wound response genes in breast cancer will improve the risk assessment of breast cancer patients and better guide patients to appropriate therapies.

描述（由申请人提供）：人体具有巨大的愈合能力，但是细胞生长，再生组织和招募新血管的能力也可能在癌症进展过程中被滥用。在许多常见的癌症，尤其是乳腺癌中，肿瘤在伤口反应模型中正常观察到的一组512个基因的能力是随后转移和死亡的强大而准确的预测指标。与传统的临床和病理危险因素相比，512基因“伤口签名”的预后信息与传统的临床和病理风险因素更具无关。伤口特征还与先前确定的预后特征和分子标记无关。但是，涉及的大量基因使每日临床实践难以实施伤口签名。该提案的核心目标是开发将大大简化伤口签名的技术。我们建议开发两种技术针对这一目标。首先，我们将根据检测其两个调节剂基因的DNA扩增来诊断伤口特征的方法。我们最近发现的是，伤口签名是两个关键生长调节基因扩增的结果，该基因预测，测量调节基因的基因将足以诊断伤口特征并预测患者的预后。其次，我们将开发一种新型的基因拾取算法和RNA扩增技术，该技术可以通过仅测量来自肿瘤样品的基因转录本的一小部分来重现伤口特征的预后能力。在资金期结束时，我们设想有能力从标准的福尔马林固定，石蜡嵌入的肿瘤切片中诊断伤口签名。乳腺癌是美国女性癌症死亡的第二大最常见原因。这些死亡通常是由乳腺癌扩散到人体其他部位的原因，该过程涉及通常用于伤口愈合的基因。改进的技术以鉴定乳腺癌的伤口反应基因将改善乳腺癌患者的风险评估，并更好地指导患者进行适当的疗法。