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方法的建立 目前迫切需要一种能够全面描述人的基因特征的检测方法。 非肌肉浸润性膀胱癌(NMIBC)用于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%的BC病例 被诊断为尿路上皮癌，75%为NMIBC。治疗方法和预后如下 NMIBC和肌肉浸润性膀胱癌(MIBC)之间有很大的区别。使用有限的 根据分子特征的不同，对NMIBC和MIBC进行了分类 侵袭深度，这不足以提供可靠的结果预测或治疗指导。 NMIBC是尿路上皮癌的一种异质性亚型(0期和1期)， 具有高复发率和疾病进展率(两年内高达40%)的特点 在所有病例中，大约10%的病例进展为MIBC)。癌症是一种 基因组；因此，BC的遗传特征应该是对其诊断、分期最确定的 分型和治疗指导。尿液中含有两种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 目前为止，尿液cfdna的检测还不能用于尿液bc cfdna的诊断。 和分层。JBS Science Inc.开发了一种新的、强大的尿液cfDNA分离方法 这克服了这些限制。因此，我们假设这种cfDNA分离方法将 为NMIBC建立尿液遗传液活组织检查。这样的测试将提供 综合NMIBC基因图谱以区分NMIBC和MIBC，指导疾病 管理和监控复发。在第一阶段可行性研究中提出了两个目标。 目标1是开发一种BC靶向的、基于杂交的NGS检测和数据分析管道。 目的2是比较组织/尿和组织/血浆变异的一致性。此外，a 将对NGS测试的可行性进行初步分析 区分NMIBC和MIBC。这项第一阶段研究的成功将证明其可行性 开发一种可用于全面的NMIBC基因特征的尿液测试 用于结直肠癌的诊断、复发监测和鉴别诊断。