BIOMEDICAL (BASIC)

生物医学（基础）

• 批准号: 7938473
• 负责人: MARTIN MCINTOSH
• 金额: $ 56.8万
• 依托单位: FRED HUTCHINSON CANCER RESEARCH CENTER
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-01-15 至 2011-01-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7938473
• 关键词: BIOMEDICAL; BASIC

We propose to use state of the art proteomics technologies and novel computational strategies to identify serum proteins that can detect the majority of women with serous ovarian cancer (SOC) three years before diagnosis. The rationale for our research plan follows from a set of factors, demonstrated in our preliminary work, which suggest that for SOC discovering biomarkers in plasma is feasible with the technologies and methodologies at our disposaL. These factors include the evidence that some serum proteins in SOC elevate two or more years before clinical diagnosis, and that our proteomics technologies are capable of identifying and measuring changes in the blood following OC development. Our research strategy is based on a hypothesis that the best performing biomarkers wil likely be those that measure the direct consequence of molecular alterations distinguishing ovarian cancer from normal cells and tissues, or even better, protein or peptide sequences that may be unique to women with OC. To identify these proteins we combine a proteomics approach capable of quantifying proteins below 1 ng/ml with unique data mining strategies that combine our SOC data with several other valuable sources of data, including: proteomic profiles of WHI blood from cancer-free women, and proteomic and genomic sequence and expression data measuring normal and tumor ovary cells. Together these data will permit us to identify which plasma proteins are possibly tumor derived, and low abundant in cancer-free women.

我们建议使用最先进的蛋白质组学技术和新的计算策略来鉴定血清蛋白，这些血清蛋白可以在诊断前三年检测出大多数患有浆液性卵巢癌（SOC）的女性。我们的研究计划的基本原理来自一系列因素，这些因素在我们的初步工作中得到证明，这表明对于SOC，利用我们掌握的技术和方法在血浆中发现生物标志物是可行的。这些因素包括有证据表明SOC中的一些血清蛋白在临床诊断前两年或两年以上升高，以及我们的蛋白质组学技术能够识别和测量OC发展后血液中的变化。我们的研究策略是基于一个假设，即表现最好的生物标志物可能是那些测量将卵巢癌与正常细胞和组织区分开来的分子改变的直接后果的生物标志物，或者更好的是，可能是OC女性特有的蛋白质或肽序列。为了识别这些蛋白质，我们将能够定量低于1 ng/ml的蛋白质的蛋白质组学方法与独特的数据挖掘策略相结合，该策略将我们的SOC数据与其他几个有价值的数据来源相结合，包括：来自无癌症女性的WHI血液的蛋白质组学谱，以及测量正常和肿瘤卵巢细胞的蛋白质组学和基因组序列和表达数据。这些数据将使我们能够确定哪些血浆蛋白可能是肿瘤来源的，并且在无癌症的女性中含量低。