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）：在美国，巴雷特食管和胃食管交界腺癌的发病率上升速度比任何其他癌症都要快。巴雷特食管 (BE) 是发生这些恶性肿瘤的高风险因素。目前我们对 BE 和食管腺癌的诊断、预防和治疗方法有限。为了对抗这种健康负担，必须采用新的途径来更好地了解这种致命癌症的发展。迫切需要开发 BE 或其后遗症患者的诊断和预后生物标志物。我们的具体目标是：目标 1：巴雷特食管和腺癌的分子分析，目标 2：分子靶标的表征和验证，目标 3：开发 BE 进展风险的诊断和预后生物标志物。本申请中提出的使用基因表达系列分析 (SAGE) 和使用高分辨率 2D 凝胶和质谱法进行蛋白质分析的全局基因表达分析将表征巴雷特食管发育的分子特征，并将它们纳入巴雷特肿瘤发生的工作模型中。我们的 mRNA 和蛋白质组分析相结合的方法将有助于发现分子生物标志物，例如编码分泌蛋白和细胞表面蛋白的基因。将继续确认扩大的功能和验证测试的生物学和临床重要性。特征性生物标志物一旦被证实对巴雷特腺癌的发展至关重要，对于改善这种致命疾病的早期诊断、预后和治疗进展具有重要的实际意义和生物学意义。此外，我们的分析将促进分子生物标志物的发现，例如编码分泌蛋白和细胞表面蛋白的基因，为血清中的生物标志物测定提供新的机会。