HCC diagnostics defined by fucosylated serum biomarkers

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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.