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: 8515943
• 负责人: MARSHA L. FRAZIER
• 金额: $ 56.12万
• 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/8515943
• 关键词: 12p; 1p35; 20q; 20q13.1; 20q13.3; Adenocarcinoma Cell; Age; Age of Onset; Antibodies; Biological Assay; Biological Markers; Biological Process; CA-19-9 Antigen; Cancer Etiology; Cancer Patient; Cancer cell line; Candidate Disease Gene; Cataloging; Catalogs; Cell Line; Chromosomes; Clinical; Complementary DNA; DNA; Detection; Development; Diagnosis; Disease; Down-Regulation; Early Detection Research Network; Early Diagnosis; Early identification; Frequencies; Gene Expression; Gene Silencing; General Population; Generations; Genes; Genetic; Genomics; Human; Hybrids; Immunohistochemistry; Individual; Length; Malignant neoplasm of pancreas; Mediating; Methods; Methylation; Microsatellite Instability; Modeling; Mutation; National Cancer Institute; Oncogenes; Pancreas; Pancreatic Adenocarcinoma; Pathway Analysis; Pathway interactions; Phase; Population; Predictive Value; Process; Proteomics; Reverse Transcriptase Polymerase Chain Reaction; Risk; Risk Assessment; Role; Sampling; Sensitivity and Specificity; Serum; Small Interfering RNA; Staging; Techniques; Time; Tumor Cell Line; Tumor Suppressor Genes; Tumor Suppressor Proteins; Tumor Tissue; United States; Validation; base; cancer initiation; cancer risk; carcinogenesis; comparative genomic hybridization; design; functional genomics; genetic profiling; human STK6 protein; loss of function mutation; matrigel; mortality; novel; outcome forecast; pancreatic cancer cells; pancreatic juice; pancreatic neoplasm; population based; research study; screening; tool; transcriptomics; tumor; tumor progression; 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）：迫切需要用于早期检测胰腺癌的生物标志物。然而，尚未发现具有基于人群的筛查所需的敏感性和特异性的单个分子。 CA-19-9 已被广泛研究，但未能证明早期检测和诊断所需的预测价值。尽管已经利用了许多平台，包括蛋白质组学、基因组学和转录组学方法，并鉴定了候选生物标志物，但没有一种平台或分子在大规模群体筛选中得到成功验证。作为国家癌症研究所早期检测研究网络的一部分，我们正在采取有针对性的方法来组建一组候选生物标志物，因为没有一种生物标志物显示出早期检测的希望。我们假设，通过鉴定胰腺癌中最早的异常遗传途径，可以发现一组胰腺癌的早期检测生物标志物。我们进一步假设涉及具有功能缺失突变/缺失的肿瘤抑制基因和显性激活/扩增/过度表达的癌基因的遗传途径是胰腺肿瘤早期发展的关键决定因素。项目 1 正在利用功能基因组学方法来发现生物标志物，并针对胰腺癌肿瘤发生的染色体 3p12 途径。三个独立的表达平台已被用来开发一组在胰腺肿瘤/正常样本中差异表达的基因，这些基因代表 3p 通路中的潜在基因以及新型肿瘤抑制因子/极性调节因子 DEAR1 被定性为胰腺癌生物标志物。项目 2 正在利用集成的功能基因组学和通路网络分析方法检查拷贝数改变的基因和 miRNA 作为早期检测生物标志物。项目 3 正在检查 1000 名胰腺癌患者的 1,536 个 SNP 和相关协变量，以开发风险模型来识别那些最有可能在早期患胰腺癌的个体，并可以使用项目一和项目二中开发的生物标志物组进行分层筛查。