HCC diagnostics defined by fucosylated serum biomarkers

描述（由申请人提供）：我们的总体目标是开发一种早期检测肝癌（肝细胞癌（HCC））的诊断测试，比现有的已批准的诊断测试和程序更具特异性和敏感性。使用糖蛋白组学发现方法，我们确定了几种糖蛋白，其血清数量和聚焦程度似乎与HCC的诊断相关。在第一阶段，按计划，我们对三种最有希望的检测标志物进行了广泛的评估，这些标志物是根据它们在检测早期HCC的能力方面优于AFP（护理标准）而选择的。此外，按照计划，我们已经成功开发了一种高通量兼容的凝集素elisa，用于非常有前途的标记物岩藻糖基化(Fc)-激肽原。在第一阶段，我们开发并验证了一种针对Fc-Kininogen的凝集素elisa，并产生了初步的、预验证的数据，证明这是一种高度敏感和选择性的早期HCC标志物。在预验证研究中，我们的Fc-Kininogen凝集素- elisa检测灵敏度为93%，特异性为90%，阳性预测值（PPV）为93%，阴性预测值（NPV）为90%，远远超过标准AFP检测的性能。这些结果满足了我们进入第二阶段的“开始”决定的标准。在II期，更大规模的验证研究将使用大量的系列和横断面患者人群，并将Fc-Kininogen测定产生的数据与现有的AFP诊断测定进行比较，以产生新的HCC体外诊断测试上市前批准所需的临床数据。我们打算与一家可以为我们生产、销售和分销商业化验的商业合作伙伴合作，并已与一家主要的美国诊断公司启动商业化讨论。实现这些目标将允许引入一种高灵敏度和特异性的诊断工具，用于HCC的早期检测。考虑到需要对HCC进行早期诊断以促进早期有效的干预，引入一种新的无创、高通量、高灵敏度和特异性诊断的血清检测方法是非常重要的。HCC诊断由集中的血清生物标志物定义。早期诊断和干预对于减少肝癌相关死亡人数至关重要。我们已经发现了新的生物标志物，并完成了I期应用的分析开发工作。在这个II期，我们建议开发和验证一种无创、高灵敏度和选择性的肝癌早期诊断测试，该测试可能适用于HBV或HCV阳性和阴性患者。我们的最终目标是开发一种早期检测诊断方法，可以作为肝癌高风险患者的常规临床筛查。

DESCRIPTION (provided by applicant): Our over-all goal has been to develop a diagnostic test for the early detection of liver cancer (hepatocellular carcinoma (HCC)) that is more specific and sensitive than existing, approved diagnostic tests and procedures. Using glycoproteomic discovery methods, we identified several glycoproteins whose serum amounts and degree of fucosylation appear to correlate with a diagnosis of HCC. In Phase I, as planned, we conducted extensive evaluations of three of the most promising detection markers which were selected based on their out-performance of AFP, the standard of care, in their ability to detect early-stage HCC. In addition, as planned, we have succeeded in developing a high throughput- compatible, lectin-ELISA for the highly promising marker Fuccosylated (Fc)-Kininogen. In phase I, we developed and validated a lectin-ELISA for Fc-Kininogen and generated preliminary, pre-validation data that demonstrate that this is a highly sensitive and selective marker for early-stage HCC. In pre-validation studies, our Fc-Kininogen lectin-ELISA assay had a sensitivity of 93%, a specificity of 90%, a positive predictive value (PPV) of 93% and a negative predictive value (NPV) of 90%, far exceeding the performance of the standard AFP assay. These results satisfied the criteria for our "Go" decision to proceed to Phase II. In phase II, larger scale validation studies will be performed using a large serial and cross sectional patient population, and data generated with the Fc-Kininogen assay will be compared with the existing AFP diagnostic assay to generate the clinical data needed for pre-market approval of a new in vitro diagnostic test for HCC. We intend to work with a commercial partner that can manufacture, market and distribute the commercial assay for us and have already initiated commercialization discussions with a major U.S. diagnostics company. Accomplishing these aims will permit the introduction of a highly sensitive and specific diagnostic tool for the early detection of HCC. Given the need for early diagnosis for HCC to facilitate early and efficacious intervention, the introduction of a new non-invasive, high throughput, highly sensitive and specific diagnostic based serum assay is extremely important.HCC Diagnostics defined by fucosylated serum biomarkers. Diagnosis and intervention at an early stage is critical to reducing the number of liver cancer-related deaths. We have discovered novel biomarkers and completed the assay development work in our phase I application. In this phase II, we propose to develop and validate a noninvasive, highly sensitive and selective early diagnostic test for liver cancer that can potentially be applicable to HBV or HCV positive and negative patients. Our ultimate goal is to develop an early detection diagnostics that can be used as a routine clinical screen in patients with high risk for developing liver cancer.