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.

非肌层浸润性膀胱癌尿液基因检测方法的建立 迫切需要一种能够全面遗传表征的测试， 非肌肉浸润性膀胱癌（NMIBC），以指导治疗和复发监测。 膀胱癌（BC）是美国第六大常见癌症。约90%的BC病例 75%的患者在诊断时为NMIBC。治疗和治疗是 NMIBC和肌肉浸润性膀胱癌（MIBC）之间有很大不同。有限的 区分分子特征，NMIBC和MIBC基于形态学分类， 侵入深度，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类（0期和1期）， 以高复发率和疾病进展率为特征（2年内高达40%）， 初步治疗，大约10%的病例进展为MIBC）。癌症是一种 基因组;因此，BC遗传特征应该是其诊断，分期， 分类和治疗指导。尿液已被证明含有两种BC肿瘤细胞 和无细胞DNA（cfDNA）。然而，尿液基质的复杂性和低浓度 迄今为止，尿CfDNA的高通量分析排除了尿BC CfDNA分析用于诊断的应用 和分层。JBS Science Inc.开发了一种新的，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 使得能够开发用于NMIBC的尿遗传液体活检。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，并监测复发。第一阶段可行性研究提出了两个目标。 目的1是开发一种BC靶向的、基于杂交的NGS测定和数据分析管道。 目的2是比较组织/尿液和组织/血浆变体一致性。另外还有按 将对NGS试验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 开发一种尿液检测，用于全面的NMIBC遗传特征， 用于BC诊断、复发监测以及区分NMIBC和MIBC。