Development of a Urine Genetic Test for NonMuscle Invasive Bladder Cancer

非肌肉浸润性膀胱癌尿液基因检测的开发

• 批准号: 10759106
• 负责人: Selena Lin
• 金额: $ 40.65万
• 依托单位: JBS SCIENCE, INC.
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-01 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10759106
• 关键词: Aftercare; American; Biological Assay; Biopsy; Cancer Patient; Capital; Classification; Clinical; Cystoscopy; Cytology; DNA; DNA Sequence Alteration; DNA analysis; Development; Diagnosis; Diagnostic; Disease; Disease Management; Disease Progression; Disease stratification; Enrollment; Feasibility Studies; Gene Frequency; Genetic; Genetic Materials; Genome; Health; Hospitals; Image; Invaded; Malignant Neoplasms; Malignant neoplasm of urinary bladder; Methods; Molecular; Monitoring for Recurrence; Morphology; Mutation; Oligonucleotides; Patient Monitoring; Patients; Phase; Plasma; Plasma Cells; Positioning Attribute; Prognosis; Recurrence; Recurrent Malignant Neoplasm; Research Design; Risk; Sample Size; Sampling; Science; Sensitivity and Specificity; Specificity; Staging; Stratification; Testing; Tissues; Transitional Cell Carcinoma; Urine; Variant; assay development; cancer classification; cancer diagnosis; cancer genetics; cancer recurrence; cancer therapy; cell free DNA; comparative; cost; data analysis pipeline; genetic analysis; genetic profiling; genetic testing; genetic variant; high risk; liquid biopsy; muscle invasive bladder cancer; neoplastic cell; non-muscle invasive bladder cancer; novel; outcome prediction; phase 1 study; success; tumor; urinary; urologic; variant detection

Development of a Urine Genetic Test for Non-Muscle-Invasive Bladder Cancer There is an urgent unmet need for a test capable of comprehensive genetic characterization of non-muscle-invasive bladder cancer (NMIBC) to guide treatment and for recurrence surveillance. Bladder cancer (BC) is the 6th most common cancer in the US. Approximately 90% of BC cases are urothelial carcinoma and 75% are NMIBC at diagnosis. The treatments and prognoses are very different between NMIBC and muscle-invasive bladder cancer (MIBC). With limited distinguishing molecular features, NMIBC and MIBC are classified based on the morphology and depth of invasion, which is insufficient for reliable outcome prediction or treatment guidance. NMIBC is a heterogeneous subclassification (stages 0 and 1) of urothelial carcinoma and is characterized by high rates of recurrence and disease progression (as high as 40% within 2 years of initial treatment, with roughly 10% of all cases progressing to MIBC). Cancer is a disease of the genome; thus, BC genetic features should be the most definitive for its diagnosis, staging subclassification, and treatment guidance. Urine has been shown to contain both BC tumor cells and cell-free DNA (cfDNA). However, the complexity of the urine matrix and the low concentration of urinary cfDNA have so far precluded the application of urine BC cfDNA analysis for diagnosis and stratification. JBS Science Inc. has developed a novel, robust urine cfDNA isolation method that overcomes these limitations. We thus hypothesize that this cfDNA isolation method will enable the development of a urine genetic liquid biopsy for NMIBC. Such a test will provide comprehensive NMIBC genetic profiling to distinguish NMIBC from MIBC, guide disease management, and monitor recurrence. Two aims are proposed in this phase I feasibility study. Aim 1 is to develop a BC-targeted, hybridization-based NGS assay and data analysis pipeline. Aim 2 is to compare the tissue/urine and tissue/plasma variant concordances. In addition, a preliminary analysis will be performed of the feasibility of the NGS test being capable of distinguishing NMIBC from MIBC. The success of this phase I study will demonstrate the feasibility of developing a urine test for comprehensive NMIBC genetic characterization that can be used for BC diagnosis, recurrence monitoring, and distinguishing NMIBC from MIBC.

开发非肌肉侵入性膀胱癌的尿液基因检测 紧急未满足的测试需要全面的遗传表征 非肌肉侵入性膀胱癌（NMIBC）指导治疗和复发监测。 膀胱癌（BC）是美国第六大最常见的癌症。约90％的卑诗省案件 尿路上皮癌和75％是诊断时的NMIBC。治疗和预后是 NMIBC和肌肉侵入性膀胱癌（MIBC）之间非常不同。有限 区分分子特征，NMIBC和MIBC是根据形态和 入侵深度，这不足以进行可靠的结果预测或治疗指导。 NMIBC是尿路上皮癌的异质亚分（第0和1阶段），为 以高复发和疾病进展的速度（2年内高达40％）的特征 初始治疗，大约有10％的所有病例发展为MIBC）。癌症是 基因组；因此，卑诗省的遗传特征应该是其诊断最明确的，分期应该是 子分类和治疗指导。尿液已显示出两个BC肿瘤细胞 和无细胞DNA（CFDNA）。但是，尿液基质和低浓度的复杂性 到目前为止，尿液CFDNA的应用排除了尿液BC CFDNA分析的应用 和分层。 JBS Science Inc.开发了一种新颖的尿液CFDNA隔离方法 这克服了这些局限性。因此，我们假设这种CFDNA隔离方法将 为NMIBC启用尿液遗传液体活检的发展。这样的测试将提供 全面的NMIBC基因分析，以区分NMIBC和MIBC，指导疾病 管理和监视复发。在此I阶段可行性研究中提出了两个目标。 AIM 1是开发基于BC的基于杂交的NGS分析和数据分析管道。 目标2是比较组织/尿液和组织/血浆变体一致性。另外， 将对NGS测试的可行性进行初步分析 将NMIBC与MIBC区分开。这一阶段I研究的成功将证明可行性 为可以使用的全面NMIBC遗传特征开发尿液测试 用于BC诊断，重复监测和将NMIBC与MIBC区分开。