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开发将极大地提高生存率。大多数女性都患有晚期疾病，存活率约为20%。蛋白质组学领域的进展为有效分析血清蛋白质组提供了必要的工具，这些技术的应用为确定新的生物标志物带来了巨大的希望。这项建议概述了全面发现、识别、量化和验证一组特异和敏感的卵巢癌生物标记物以进行早期检测的方法。我们提出了以下具体目标： 1.通过血清综合生物标志物分析确定候选卵巢癌生物标志物。重点将放在完善全面和可重复测量的最有效的总体分析战略上。最准确地区分癌症和对照的光谱峰值将使用高分辨率技术来识别。将使用生物统计学和生物信息学来确定候选标记的优先顺序(根据特异性、敏感性和预测值)，以便进一步确定特征。 2.候选生物标志物的识别和绝对定量。这将在随后的验证测试中提高可靠性和高通量能力，这些蛋白质的鉴定将有助于进一步研究疾病的生物学基础。我们将使用精确的质量测量、串联质谱学和非冗余的蛋白质和基因组数据库应用于不同的选定对照。此外，我们将使用稳定同位素标记的内标来确定正常和癌症血清样本的取值范围。 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被用来准确地确定在疾病的各个方面(早期/晚期、家族性、缓解和复发)和在大量非癌症对照中，个人和候选标记物的组合的敏感性、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.