Biomarkers in Barrett's Tumorigenesis

巴雷特肿瘤发生中的生物标志物

• 批准号: 7168788
• 负责人: WAEL EL-RIFAI
• 金额: $ 33.82万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-03-20 至 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7168788
• 关键词: Barretts esophagus; SCID mouse; adenocarcinoma; athymic mouse; biomarker; cancer risk; carcinogenesis; clinical research; esophagogastric junction; esophagus neoplasm; gastric mucosa; gene expression; genetic mapping; human tissue; immunocytochemistry; neoplastic process; northern blottings; oral mucosa; protein quantitation /detection; proteomics; serial analysis of gene expression; two dimensional gel electrophoresis; western blottings

DESCRIPTION (provided by applicant): The incidence of Barrett's esophageal and gastro-esophageal junctional adenocarcinoma is rising faster than that of any other cancer in the United States. Barrett's Esophagus (BE) is a high risk factor for developing these malignancies. Our diagnostic, preventive, and therapeutic approaches to BE and esophageal adenocarcinoma are currently limited. In order to combat this health burden, novel avenues to better understand this lethal cancer's development must be employed. The development of diagnostic and prognostic biomarkers for patients with BE or its sequalae is desperately needed. Our specific aims are: Aim 1: Molecular profiling of Barrett's esophagus and adenocarcinoma, Aim 2: Characterization and validation of molecular targets and Aim 3: Development of diagnostic and prognostic biomarkers for BE progression risk. Global gene expression analyses using serial analysis of gene expression (SAGE) and protein profiling using high resolution 2D gels and mass spectrometry as proposed in this application will characterize the molecular signatures for the development of Barrett's esophagus and incorporate them into a working model of Barrett's tumorigenesis. Our combined mRNA and proteomic analysis approaches will facilitate the discovery of molecular biomarkers such as genes encoding secreted and cell surface proteins. Confirmation of biological and clinical importance in expanded functional and validation testing will be continued. Signature biomarkers once validated as critical in Barrett's adenocarcinoma development have important practical as well as biological implications for improved early diagnostic, prognostic, and therapeutic advances in this lethal disease. Moreover, our analyses will facilitate the discovery of molecular biomarkers such as genes encoding secreted and cell surface proteins providing new opportunities for biomarker assays in the serum.

描述（由申请人提供）：巴雷特的食管和胃食管连接腺癌的发生率比美国其他任何癌症都快。巴雷特的食管（BE）是发展这些恶性肿瘤的高风险因素。目前，我们的诊断性，预防和治疗方法和食管腺癌目前受到限制。为了应对这种健康负担，必须采用新的途径来更好地了解这种致命的癌症的发展。迫切需要针对患有BE或其序列的患者的诊断和预后生物标志物的开发。我们的具体目的是：目标1：Barrett食管和腺癌的分子分析，AIM 2：分子靶标的表征和验证和目标3：开发诊断和预后生物标志物，以成为进展风险。全局基因表达分析使用本应用中提出的高分辨率2D凝胶和质谱高的基因表达（SAGE）和蛋白质分析的序列分析将表征用于开发Barrett食管的分子特征，并将它们掺入Barrett肿瘤的工作模型中。我们组合的mRNA和蛋白质组学分析方法将促进发现分子生物标志物，例如编码分泌的基因和细胞表面蛋白。将继续确认生物学和临床重要性在扩展的功能和验证测试中。签名生物标志物曾经在巴雷特的腺癌发育中被证实是至关重要的，对这种致命疾病的早期诊断，预后和治疗进步具有重要的实用和生物学意义。此外，我们的分析将有助于发现分子生物标志物，例如编码分泌的基因和细胞表面蛋白，从而为血清中的生物标志物分析提供了新的机会。