An integrated systems biology approach for ovarian cancer biomarker discovery

描述（由申请人提供）：现在有令人信服的证据表明，早期癌症检测可以通过早期治疗获得更好的患者结局。早期诊断癌症的最佳方法之一是使用血清生物标志物。不幸的是，对于大多数癌症，我们没有有效的生物标志物用于早期检测或预测治疗反应。通过这项拨款申请，我们的目标是确定卵巢癌的生物标志物-美国最致命的妇科恶性肿瘤。这项资助申请的主要目的是检查一组新发现的卵巢癌生物标志物（通过集成系统生物学蛋白质组学方法），与经典的卵巢癌生物标志物CA 125和其他9种有前途的生物标志物（如HE 4和一组激肽释放酶）组合，是否构成了一种新的多参数血清组，用于早期卵巢癌诊断，具有高灵敏度和特异性。通过采用免疫测定和基于免疫质谱的技术，我们将对我们的前40种新型生物标志物进行I期临床前研究，我们将仅选择特异性为98%和灵敏度为30%的生物标志物进行II期评估。II期病例对照研究，使用作为该资助申请的一部分开发的经验证的免疫测定法，将利用PRoBE研究设计进行样品收集，并且只有那些显示至少98%特异性和至少70%灵敏度的标志物将进行使用EDRN CVC卵巢癌参考样品集的独立盲法研究。预计2-4个新的候选者，沿着与10个已知标志物中的一些一起，将构成具有高特异性和灵敏度的多参数组，适用于卵巢癌的早期诊断和可能的筛查。

DESCRIPTION (provided by applicant): There is now convincing evidence that early cancer detection can lead to better patient outcomes through early administration of therapy. One of the best ways to early diagnose cancer is to use serum biomarkers. Unfortunately, for most cancers, we do not have effective biomarkers for either early detection or prediction of therapeutic response. With this grant application, we aim to identify such biomarkers for ovarian cancer - the most lethal gynecological malignancy in the United States. The major objective of this grant application is to examine if a panel of newly discovered ovarian cancer biomarkers (via an integrated systems biology proteomic approach), in combination with the classical ovarian cancer biomarker, CA125 and 9 other promising biomarkers such as HE4 and a group of kallikrein enzymes, constitutes a new, multiparametric serum panel for early ovarian cancer diagnosis with high sensitivity and specificity. By employing immunoassays and immuno-mass spectrometry-based technologies, we will perform a Phase I preclinical study on our top 40 novel biomarkers from which we will select only those displaying 98% specificity and 30% sensitivity for Phase II evaluation. The Phase ll case-control study, using validated immunoassays developed as part of this grant application, will utilize the PRoBE study design for sample collection and only those markers displaying at least 98% specificity and at least 70% sensitivity will proceed for an independent, blinded study using the EDRN CVC ovarian cancer reference sample set. It is anticipated that 2-4 new candidates, along with some of the 10 known markers will constitute a multiparametric panel with high specificity and sensitivity, suitable for early diagnosis and possible screening for ovarian cancer.