Development of a urine test for the early detection of liver cancer

开发用于早期发现肝癌的尿液检测

• 批准号: 10006054
• 负责人: Selena Lin
• 金额: $ 100万
• 依托单位: JBS SCIENCE, INC.
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-07-01 至 2023-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10006054
• 关键词: AFP gene; Automation; Award; Biological Assay; Biological Markers; Blinded; Blood Circulation; Businesses; Cancer Etiology; Categories; Certification; Cessation of life; Clinical; Collaborations; Collection; Current Procedural Terminology Codes; DNA Markers; Data; Development; Disease; Drops; Early Diagnosis; Edetic Acid; Epigenetic Process; Evaluation; Funding; Genetic; Goals; Guidelines; Hepatology; Hour; Journals; Laboratories; Malignant Neoplasms; Malignant neoplasm of liver; Manuscripts; Measures; Medical; Methods; Modification; Non-Invasive Cancer Detection; Organ; Patients; Performance; Phase; Populations at Risk; Primary Malignant Neoplasm of Liver; Procedures; Professional Organizations; Protocols documentation; Publishing; Recurrence; Risk; Science; Screening for Hepatocellular Cancer; Serum; Standardization; Survival Rate; Temperature; Testing; Transportation; Urine; Validation; alpha-Fetoproteins; base; cell free DNA; clinical research site; commercialization; effective therapy; improved; liquid biopsy; outcome forecast; performance tests; phase 2 study; precision medicine; public health relevance; screening; standard of care; success; tumor DNA; validation studies

Development of a urine test for the early detection of liver cancer The need to develop an effective method for detecting liver cancer is urgent. HCC, a primary liver cancer, is the third leading cause of cancer deaths worldwide and the fastest rising cancer in US. HCC has a 5-year survival rate of less than 15%, if detected early, the survival rate can be as high as 40%. The survival rate drops significantly, however, to as low as 2% if the cancer has spread to other organs. We have successfully accomplished the proposed milestones from our Phase II award (5R44CA165312-04) to develop an HCC screening test (the JBS HCC test) that can identify 30% more HCC than serum AFP, the current most used biomarker for HCC screening. This phase IIB application is to bridge the gap between our successful accomplishments in the Phase II period and commercialization of the JBS HCC test for HCC screening, so more people with HCC can benefit from early detection. The early detection of HCC is critical for the effective treatment and cure of this disease. Although the JBS test shows great promise to improve liver cancer screening, there are steps (identified as milestones in this application) that need to be taken before the test can reach at-risk patients for HCC. These steps include CLIA certification (Aim 1) so that the test can be marketed as a laboratory developed test (LDT), and filing request for a CPT code for the third party payee reimbursement, and evaluation of performance through a multicenter, blinded validation study to generate data supporting clinical benefit so the test can be considered as a standard of care for HCC screening in at-risk populations (Aim 2), and standardization of urine collection, storage, and transportation, and automation of urine cfDNA isolation to facilitate commercialization (Aim 3). Thus, three specific Aims are proposed to prepare for the launch of the JBS HCC screening test to the market.

肝癌早期尿液检测方法的建立 迫切需要开发一种检测肝癌的有效方法。HCC，原发性肝脏 癌症是全球癌症死亡的第三大原因，也是美国增长最快的癌症。 肝癌的5年生存率低于15%，如果早期发现，生存率可以很高 40%。然而，如果癌症已经扩散到20%，存活率会显著下降， 其他器官。我们已经成功地完成了第二阶段提出的里程碑 授予（5 R44 CA 165312 -04）开发HCC筛查测试（JBS HCC测试），可以识别 HCC比血清AFP多30%，血清AFP是目前最常用的HCC筛查生物标志物。这个阶段 IIB的申请是为了弥合我们在第二阶段取得的成功之间的差距 和商业化的JBS肝癌检测肝癌筛查，使更多的人与肝癌， 受益于早期发现。肝癌的早期发现是有效治疗的关键， 治愈这种疾病。虽然JBS测试显示出很大的希望，以改善肝癌筛查， 在测试之前需要采取一些步骤（在本应用程序中标识为里程碑） 可以接触到有肝癌风险的患者。这些步骤包括CLIA认证（目标1）， 可以作为实验室开发的测试（LDT）销售，并申请CPT代码， 第三方收款人报销，并通过多中心、盲态 验证研究，以生成支持临床获益的数据，因此该试验可被视为 在高危人群中进行HCC筛查的护理标准（目标2），以及尿液标准化 收集、储存和运输，以及尿cfDNA分离的自动化，以促进 商业化（目标3）。因此，提出了三个具体目标，为发射做准备。 JBS HCC筛查试验推向市场。

项目成果

ChimericSeq: An open-source, user-friendly interface for analyzing NGS data to identify and characterize viral-host chimeric sequences.

ChimericSeq：一个开源，用户友好的接口，用于分析NGS数据以识别和表征病毒宿主嵌合序列。

• DOI: 10.1371/journal.pone.0182843
• 发表时间: 2017
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Shieh FS;Jongeneel P;Steffen JD;Lin S;Jain S;Song W;Su YH
• 通讯作者: Su YH

A New Method for Improving Extraction Efficiency and Purity of Urine and Plasma Cell-Free DNA.

• DOI: 10.3390/diagnostics11040650
• 发表时间: 2021-04-03
• 期刊: Diagnostics (Basel, Switzerland)
• 作者: Lin SY;Luo Y;Marshall MM;Johnson BJ;Park SR;Wang Z;Su YH
• 通讯作者: Su YH

Development and Evaluation of Novel Statistical Methods in Urine Biomarker-Based Hepatocellular Carcinoma Screening.

• DOI: 10.1038/s41598-018-21922-9
• 发表时间: 2018-02-28
• 期刊: Scientific reports
• 影响因子: 4.6
• 作者: Wang J;Jain S;Chen D;Song W;Hu CT;Su YH
• 通讯作者: Su YH

Detection of Hepatitis B Virus-Host Junction Sequences in Urine of Infected Patients.

• DOI: 10.1002/hep4.1783
• 发表时间: 2021-10
• 期刊: Hepatology communications
• 影响因子: 5.1
• 作者: Lin SY;Su YP;Trauger ER;Song BP;Thompson EGC;Hoffman MC;Chang TT;Lin YJ;Kao YL;Cui Y;Hann HW;Park G;Shieh FS;Song W;Su YH
• 通讯作者: Su YH

Comprehensive DNA methylation analysis of hepatitis B virus genome in infected liver tissues.

感染肝组织中丙型肝炎病毒基因组的全面DNA甲基化分析。

• DOI: 10.1038/srep10478
• 发表时间: 2015-05-22
• 期刊: Scientific reports
• 影响因子: 4.6
• 作者: Jain S;Chang TT;Chen S;Boldbaatar B;Clemens A;Lin SY;Yan R;Hu CT;Guo H;Block TM;Song W;Su YH
• 通讯作者: Su YH