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.

非肌肉浸润性膀胱癌尿液基因检测的开发 目前迫切需要一种能够全面表征遗传特征的测试 非肌层浸润性膀胱癌 (NMIBC) 指导治疗和复发监测。 膀胱癌 (BC) 是美国第六大常见癌症。大约 90% BC 病例 诊断时 75% 为尿路上皮癌，75% 为 NMIBC。治疗方法和预后是 NMIBC 和肌层浸润性膀胱癌 (MIBC) 之间有很大不同。与有限的 根据分子特征，NMIBC 和 MIBC 根据形态和结构进行分类 侵袭深度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类（0 期和 1 期）， 其特点是复发率和疾病进展率高（2年内高达40%） 初始治疗期间，大约 10% 的病例进展为 MIBC）。癌症是一种疾病 基因组；因此，BC 的遗传特征对于其诊断、分期来说应该是最明确的 细分和治疗指导。尿液已被证明含有两种 BC 肿瘤细胞 和游离 DNA (cfDNA)。但尿液基质复杂且浓度低 迄今为止，尿液 cfDNA 的检测排除了尿液 BC cfDNA 分析在诊断中的应用 和分层。 JBS Science Inc. 开发了一种新型、稳健的尿液 cfDNA 分离方法 克服了这些限制。因此，我们假设这种 cfDNA 分离方法将 开发用于 NMIBC 的尿液遗传液体活检。这样的测试将提供 全面的 NMIBC 基因分析，区分 NMIBC 和 MIBC，指导疾病 管理，并监测复发情况。第一阶段可行性研究提出了两个目标。 目标 1 是开发一种针对 BC 的、基于杂交的 NGS 检测和数据分析流程。 目标 2 是比较组织/尿液和组织/血浆变异一致性。此外，一个 将对NGS测试的可行性进行初步分析 区分 NMIBC 和 MIBC。第一阶段研究的成功将证明可行性 开发可用于综合 NMIBC 遗传特征的尿液检测 用于 BC 诊断、复发监测以及区分 NMIBC 和 MIBC。