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带来更好的患者结果。早期诊断癌症的最好方法之一是使用血清生物标记物。不幸的是，对于大多数癌症，我们没有有效的生物标志物来早期发现或预测治疗反应。通过这项拨款申请，我们的目标是确定卵巢癌的此类生物标记物--美国最致命的妇科恶性肿瘤。这项拨款申请的主要目的是检验一组新发现的卵巢癌生物标记物(通过综合系统生物学蛋白质组方法)，与经典的卵巢癌生物标记物、CA125和其他9种有希望的生物标记物，如HE4和一组激肽释放酶，是否构成一个新的、具有高敏感性和特异性的早期卵巢癌多参数血清标记物。通过使用免疫分析和基于免疫质谱学的技术，我们将对我们的前40个新生物标记物进行I期临床前研究，从中我们将只选择那些显示98%特异性和30%敏感性的生物标记物进行II期评估。作为这项赠款申请的一部分，二期病例对照研究使用了经过验证的免疫分析方法，将利用探针研究设计进行样本收集，只有那些显示至少98%特异性和至少70%敏感性的标记物才会使用EDRN CVC卵巢癌参考样本集进行独立的盲法研究。预计2-4个新的候选者以及10个已知标记物中的一些将构成一个具有高特异性和敏感性的多参数小组，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.