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比现有的、经批准的诊断测试和程序更具特异性和敏感性的肝癌(肝细胞癌)早期检测诊断测试。利用糖蛋白质组发现方法，我们鉴定了几种糖蛋白，它们的血清量和岩藻糖化程度似乎与肝细胞癌的诊断相关。在第一阶段，我们按计划对三个最有希望的检测标记物进行了广泛的评估，这些标记物是根据它们在检测早期肝癌方面的表现优于AFP(护理标准)而选择的。此外，按照计划，我们已经成功地开发了一种高通量兼容的凝集素-ELISA，用于非常有前景的标记岩藻糖化(Fc)-激肽原。在第一阶段，我们开发并验证了Fc-Kininogen的凝集素-ELISA，并产生了初步的预验证数据，证明这是一种对早期肝细胞癌高度敏感和选择性的标记物。在预验证研究中，我们的Fc-激肽原凝集素-ELISA法的灵敏度为93%，特异度为90%，阳性预测值(PPV)为93%，阴性预测值(NPV)为90%，远远超过标准AFP检测的表现。这些结果满足了我们决定进入第二阶段的标准。在第二阶段，将使用大量连续和横断面患者群体进行更大规模的验证研究，并将FC-Kininogen分析产生的数据与现有的AFP诊断分析进行比较，以产生新的肝细胞癌体外诊断测试上市前批准所需的临床数据。我们打算与一家能够为我们制造、营销和分销商业化验的商业合作伙伴合作，并已与一家美国大型诊断公司启动了商业化谈判。实现这些目标将允许引入一种高度敏感和特异的诊断工具，用于肝癌的早期检测。鉴于对肝癌进行早期诊断以便于早期有效干预的需要，引入一种新的非侵入性、高通量、高灵敏度和特异性的基于诊断的血清检测方法是非常重要的。早期诊断和干预是减少肝癌相关死亡人数的关键。我们已经发现了新的生物标志物，并在我们的第一阶段应用中完成了测试开发工作。在这一阶段，我们建议开发和验证一种无创、高度敏感和选择性的肝癌早期诊断试验，该试验可能适用于乙肝病毒或丙型肝炎病毒阳性和阴性的患者。我们的最终目标是开发一种早期检测诊断方法，可以作为肝癌高危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.