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用于早期检测肝癌（肝细胞癌（HCC））的诊断测试，该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，我们鉴定了几种糖蛋白，其血清含量和岩藻糖基化程度似乎与肝癌的诊断相关。在第一阶段，按照计划，我们对三种最有希望的检测标志物进行了广泛的评估，这些标志物是根据其在检测早期HCC的能力方面优于AFP（标准治疗）而选择的。此外，如计划的那样，我们已经成功地开发了用于高度有前途的标记物岩藻糖基化（Fc）-激肽原的高通量相容的凝集素-ELISA。在第一阶段，我们开发并验证了Fc-激肽原的凝集素-ELISA，并产生了初步的预验证数据，证明这是早期HCC的高度敏感和选择性标志物。在预验证研究中，我们的Fc-激肽原凝集素-ELISA测定具有93%的灵敏度、90%的特异性、93%的阳性预测值（PPV）和90%的阴性预测值（NPV），远远超过标准AFP测定的性能。这些结果符合我们决定进入第二阶段的标准。在II期研究中，将使用大型系列和横断面患者人群进行更大规模的验证研究，并将Fc-激肽原检测试剂盒生成的数据与现有AFP诊断检测试剂盒进行比较，以生成新的HCC体外诊断检测试剂盒上市前批准所需的临床数据。我们打算与一家商业合作伙伴合作，该合作伙伴可以为我们制造、销售和分销商业检测试剂盒，并且已经与一家主要的美国诊断公司开始了商业化讨论。实现这些目标将允许引入一种高度敏感和特异性的诊断工具，用于早期发现HCC。鉴于需要对HCC进行早期诊断以促进早期和有效的干预，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测定是极其重要的。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，并在我们的第一阶段应用中完成了检测开发工作。在第二阶段，我们建议开发和验证一种非侵入性，高灵敏度和选择性的肝癌早期诊断测试，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，可用作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.