A novel diagnostic biomarker for Hepatocellular Carcinoma(HCC)

肝细胞癌 (HCC) 的新型诊断生物标志物

• 批准号: 8905119
• 负责人: Xuanyong Lu
• 金额: $ 63.26万
• 依托单位: IMCARE BIOTECH, INC.
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-01 至 2018-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8905119
• 关键词: Academic Medical Centers; Address; Adopted; Affect; Antibodies; Biological Markers; Biopsy; Cessation of life; Chronic Hepatitis B; Cirrhosis; Clinical; Clinical Research; Clinical Trials; Communities; Confidence Intervals; Control Groups; Data; Detection; Development; Diagnosis; Diagnostic; Disease; Double-Blind Method; Early Diagnosis; Effectiveness; Enzyme-Linked Immunosorbent Assay; Goals; Hepatitis; Hepatitis B Virus; Hepatitis C virus; Hospitals; Imaging technology; Insurance; Liver; Liver Cirrhosis; Liver diseases; Magnetic Resonance Imaging; Malignant Neoplasms; Malignant neoplasm of liver; Marketing; Medical; Medical Device; Methodology; Methods; Monitor; Monoclonal Antibodies; Names; Ohio; Pancreatitis; Patients; Performance; Phase; Physicians; Primary carcinoma of the liver cells; Procedures; Product Approvals; Proteins; Protocols documentation; Recurrence; Reproducibility; Research Personnel; Risk; Sample Size; Sampling; Sensitivity and Specificity; Serine Proteinase Inhibitors; Serum; Solutions; Specificity; Specimen; Staging; Survival Rate; System; Technology; Testing; Treatment Cost; Ultrasonography; Variant; alpha-Fetoproteins; base; cancer cell; commercialization; cost; high risk; improved; liver function; midkine; new technology; novel diagnostics; phase 1 study; phase 2 study; product development; public health relevance; research clinical testing; screening; tool; tumor

 DESCRIPTION (provided by applicant): Hepatocellular carcinoma (HCC) is usually undetected until its later stages, where the 5-year survival rate for patients is less than 10%. However, the survival rate can be as high as 40% if the cancer is detected early. Unfortunately, early detection of HCC is not possible with any screening tests that are currently available, such as ultrasound or imaging technologies. Alpha-Fetoprotein (AFP), which is currently the diagnostic marker used for HCC screening, is limited by its low specificity and lack of sensitivity Therefore, a method of detecting HCC accurately and/or in its early stages would greatly improve our ability to manage and treat the disease. Background and Objective: We aim to complete the development of HepatoDetect(r), an ELISA-based diagnostic system, which strongly confirmed its ability to identify both early and late stage Hepatocellular Carcinoma (HCC) with high sensitivity and specificity during our phase I study. The HepatoDetect(r) diagnostic kit is based on the use of a monoclonal antibody to quantitatively detect a protein specifically secreted by liver cancer cells - Liver Cancer-Serine Protease Inhibitor Kazal (LC-SPIK). The effectiveness of LC-SPIK as a marker in distinguishing HCC from other liver diseases, non-liver diseases and healthy subjects was evaluated in phase I and showed that the mean level of LC-SPIK in HCC patients (43ng/ml) was significantly higher (P < 0.001) than in patients with hepatitis, liver cirrhosis, pancreatitis and in healthy subjects (11ng/ml, 10ng/ml, 2.3ng/ml and 3.2ng/ml, respectively). Using a cut-off value of 22ng/ml, the sensitivity and specificity of serum LC-SPIK for HCC were 79% and 94% respectively, compared to only 45% and 69% for AFP. Most encouraging, LC-SPIK's accuracy in detecting very early stage HCC (tumor size < 2 cm) was 80.0%, compared to only 33% for AFP. The data clearly supports that the technology is significantly better than AFP. We are also confident that HepatoDetect(r) has significant advantages over other current screening and diagnostic methodologies, including many of those still in development. Imaging technologies (CT, MRI, Ultrasound) are operator dependent and very expensive, biopsies are invasive, and developmental technologies such as MDK (midkine) and Gp73 are less specific and are not yet validated.15-19 We propose to further optimize, validate, and complete the development of our HepatoDetect(r) diagnostic kit for clinical use in our phase II study. Procedure: Aim1: We will standardize and optimize our technology and complete development for "HepatoDetect(r) " to screen for HCC. This ELISA kit would be reliable, easy to operate, and inexpensive. Aim2: Using this kit, we will continue to systematically evaluate the performance of LC-SPIK in HCC using a large, double-blinded sample set, which includes 350 HCC specimens and 400 controls from subjects with normal livers, pancreatitis, hepatitis and cirrhosis. The ultimate goal is to receive FDA pre-market approval for this product and to commercialize it. Market: Nearly 5 million people in US and 450 million people worldwide are affected by HBV or HCV, and 30-40% of them are at a high risk of developing HCC. For these people, routine examinations for cancer are necessary. Thus there is a very large market for HCC detection and testing. Competition: Currently, the only diagnostic marker used for HCC detection is AFP, which is significantly less effective than our solution, and there are no other similar products available.

 描述：肝细胞癌（HCC）通常要直到其阶段或患者较少10％，但是，如果不幸的是，早期发现癌症的生存率可以高达40％。目前可用的测试或成像技​​术：我们旨在完成肝道路（R）的发展，在我们的II阶段研究期间，基于ELISA的诊断系统可以确定和特异性。在肝癌细胞肝癌细胞肝癌蛋白酶抑制剂KAZAL（LC-SPIK）的特异性分泌的LC-SPIK作为将HCC与其他肝肝疾病区分开的标记，非肝脏疾病和健康受试者在I期中评估，并显示出在I期中的健康受试者，并显示在HCC患者（43 ng/ml）中，LC-SPIK的THEAN水平明显更高（p <0.001）泰迪钛，肝肝硬化，胰腺炎和健康受试者（11NG/mL，10 ng/ml，2.3 ng/ml，2.3 ng/ml和ml ，重新选择和94％的人，相比之下，AFP最令人鼓舞的是，LC-Spik的精确阶段非常早（肿瘤尺寸<2 cm）显然支持该技术。比法新社更好。 15-19我们提议在我们的II阶段AIM1：供临床使用中，诸如MDK（Midkine）之类的发育技术尚未得到验证。我们将标准化和压缩“ Hepatodetect（R）”以筛选HCC。在HCC中使用正常的Libers，胰腺炎，肝炎和肝硬化的受试者中的大型ND对照。他们中有很高的风险是这些人的HCC，常规的癌症检查是HCC检测和测试的大型市场。是其他类似产品。