Ovarian Cancer Screening Using Comprehensive Proteomics

描述（由申请人提供）： 早期检测卵巢癌的生物标志物的发展将大大提高生存率。大多数妇女表现为晚期疾病，存活率约为20%。蛋白质组学领域的进展现在提供了有效分析血清蛋白质组所必需的工具，并且这些技术的应用对于确定新的生物标志物具有很大的希望。该提案概述了全面发现，识别，量化和验证一组特异性和敏感性卵巢癌生物标志物的方法，用于早期检测。我们提出以下具体目标： 1.通过血清的综合生物标志物分析确定候选卵巢癌生物标志物。重点将放在完善最有效的整体分析策略，全面和可重复的测量。将使用高分辨率技术识别最准确区分癌症与对照的光谱峰。生物统计学和生物信息学将用于优先考虑候选标记物（根据特异性、灵敏度和预测值），以进行进一步表征。 2.候选生物标志物的鉴定和绝对定量。这将提高后续验证测试的可靠性和高通量能力，这些蛋白质的鉴定将进一步有助于研究疾病的生物学基础。我们将使用精确的质量测量，串联质谱，和非冗余的蛋白质和基因组数据库应用于不同的选择控制。此外，我们将使用稳定同位素标记的内标物确定正常和癌症血清样品的值范围。 3.一组生物标志物在特定女性群体中的临床验证。来自确定的女性队列的血清将用于准确确定单个和候选标志物组合在疾病的所有方面（早期/晚期、家族性、缓解和复发）和大量非癌症对照中的灵敏度、特异性和预测值。

DESCRIPTION (provided by applicant): The development of biomarkers for earlier detection of ovarian cancer will greatly improve survival. Most women present with advanced stage disease with survival rates of roughly 20%. Advances in the field of proteomics now provide the tools necessary to effectively analyze the serum proteome, and the application of such technologies holds great promise for determining novel biomarkers. This proposal outlines methods to comprehensively discover, identify, quantify, and validate a panel of specific and sensitive ovarian cancer biomarkers for early detection. We propose the following Specific Aims: 1. Determine candidate ovarian cancer biomarkers defined by comprehensive biomarker analysis of serum. Emphasis will be placed on refining the most effective overall analytical strategy for comprehensive and reproducible measurements. Spectral peaks that most accurately distinguish cancer vs. control will be identified using high-resolving power technology. Biostatistics and bioinformatics will be used to prioritize candidate markers (according to specificity, sensitivity and predictive value) for further characterization. 2. Identification and absolute quantification of the candidate biomarkers. This will improve reliability and high-throughput capabilities in subsequent validation testing, and the identification of these proteins will contribute further to research into the biologic basis of the disease. We will use accurate mass measurements, tandem mass spectrometry, and non-redundant protein and genome databases applied to distinct selected controls. Furthermore, we will determine the range of values for both normal and cancer serum samples using stable isotope labeled internal standards. 3. Clinical validation of a panel of biomarkers in specific groups of women. Sera from defined cohorts of women will be used to accurately determine the sensitivity, specificity, and predictive values of individual and combinations of candidate markers in all aspects of disease (early/late stage, familial, remission and recurrence) and in large numbers of non-cancer controls.