Biomarkers for the Early Detection of Pancreatic Cancer

用于早期检测胰腺癌的生物标志物

• 批准号: 7983177
• 负责人: MARSHA L. FRAZIER
• 金额: $ 61.62万
• 依托单位: UNIVERSITY OF TX MD ANDERSON CAN CTR
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-28 至 2015-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7983177
• 关键词: Age; Biological Markers; CA-19-9 Antigen; Cancer Patient; Chromosomes; Development; Diagnosis; Early Detection Research Network; Early Diagnosis; Early identification; Genes; Genetic; Genomics; Individual; Malignant neoplasm of pancreas; Modeling; National Cancer Institute; Oncogenes; Pathway Analysis; Pathway interactions; Phase; Population; Predictive Value; Proteomics; Risk; Sampling; Screening procedure; Sensitivity and Specificity; Tumor Suppressor Genes; Tumor Suppressor Proteins; functional genomics; loss of function mutation; novel; pancreatic neoplasm; population based; transcriptomics; tumorigenesis

DESCRIPTION (provided by applicant): Biomarkers for the early detection of pancreatic cancer are urgently needed. However, individual molecules with the sensitivity and specificity needed for population-based screening have not been discovered. CA-19-9 has been studied extensively and yet has failed to demonstrate the predictive value necessary for early detection and diagnosis. Although many platforms, including proteomic, genomic and transcriptomic approaches have been utilized and biomarker candidates identified, no one platform or molecule has been successfully validated in large population screens. As a part of the National Cancer Institute Early Detection Research Network, we are taking a targeted approach to assemble a panel of biomarker candidates, given that no one biomarker has shown promise for early detection. We hypothesize that a panel of early detection biomarkers for pancreatic cancer could be discovered by the identification of the earliest genetic pathways aberrant in pancreatic cancer. We furthermore hypothesize that genetic pathways involving tumor suppressor genes with loss of function mutations/deletions and dominantly activated/amplified/over expressed oncogenes are critical determinants in the development of the early phases of pancreatic neoplasia. Project 1 is utilizing a functional genomics approach toward biomarker discovery and is targeting the chromosome 3p12 pathway to tumorigenesis in pancreatic cancer. Three separate expression platforms have been utilized to develop a panel of genes differentially expressed in pancreatic tumor/normal samples and which represent potential genes in the 3p pathway as well as a novel tumor suppressor/polarity regulator DEAR1 is being characterized as a pancreatic cancer biomarker. Project 2 is examining copy number altered genes and miRNAs as early detection biomarkers utilizing an integrated functional genomics and pathway network analysis approach. Project 3 is examining a panel of 1,536 SNPs and relevant covariates in 1000 pancreatic cancer patients to develop a risk model to identify those individuals most likely to develop pancreatic cancer at an early age and could be stratified for screening using biomarker panels developed in projects one and two.

描述（由申请人提供）：迫切需要早期检测胰腺癌的生物标志物。但是，尚未发现具有基于人群筛查所需的灵敏度和特异性的个体分子。 CA-19-9已经进行了广泛的研究，但未能证明早期检测和诊断所需的预测价值。尽管已经使用了许多平台，包括蛋白质组学，基因组和转录组方法并确定了生物标志物候选者，但在大型人口筛选中，没有一个平台或分子成功验证。作为国家癌症研究所早期检测研究网络的一部分，我们正在采用一种有针对性的方法来组装一组生物标志物候选者，因为没有一个生物标志物显示出早期检测的希望。我们假设，可以通过鉴定胰腺癌中最早的遗传途径异常发现胰腺癌的早期检测生物标志物。我们进一步假设，涉及功能突变/缺失损失的肿瘤抑制基因的遗传途径以及主要激活/扩增/过度表达的癌基因是胰腺肿瘤早期阶段发展的关键决定因素。项目1正在利用一种功能基因组学方法来发现生物标志物，并针对胰腺癌中肿瘤发生的3P12染色体途径。已经利用了三个独立的表达平台来开发在胰腺肿瘤/正常样品中差异表达的一组基因，它们代表了3P途径中的潜在基因，以及一种新型的肿瘤抑制剂/极性调节剂DEAR1的表现为胰腺癌生物标志物。项目2正在研究使用集成功能基因组学和途径网络分析方法的早期检测生物标志物的拷贝数改变基因和miRNA。项目3正在检查1,536个SNP的面板和1000名胰腺癌患者中相关的协变量，以开发风险模型，以识别那些最有可能在较早的年龄发展胰腺癌的人，并且可以使用项目和第二个项目中开发的生物标记面板进行筛查。