Impact of preanalytic procurement and processing variables on the detection of HCC DNA in urine

分析前采购和处理变量对尿液中 HCC DNA 检测的影响

• 批准号: 10549981
• 负责人: Ying-Hsiu Su
• 金额: $ 39.54万
• 依托单位: BARUCH S. BLUMBERG INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-02-01 至 2028-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10549981
• 关键词: AFP gene; Aftercare; Apoptotic; Biological Assay; Blood; Cancer Etiology; Cells; Centrifugation; Cessation of life; Chronic Hepatitis B; Clinic; Clinical; Clinical Data; Clinical Trials; Collection; Colon Carcinoma; DNA; DNA Maintenance; DNA Markers; DNA analysis; Detection; Early Detection Research Network; Early Diagnosis; Edetic Acid; Enrollment; Excision; Freezing; Genetic; Genomic DNA; Genomics; Goals; Guidelines; Hepatitis B Infection; Hepatitis B Virus; Hepatocyte; Home; Hour; Image; Intake; Kidney; Liquid substance; Literature; Liver; Magnetic Resonance Imaging; Malignant Neoplasms; Measurement; Methods; Molecular Weight; Monitor; National Comprehensive Cancer Network; Nodule; Patients; Performance; Primary carcinoma of the liver cells; Procedures; Process; Prognosis; Prospective Studies; Protocols documentation; Recommendation; Recovery; Recurrence; Reproducibility; Sampling; Serum; Site; Temperature; Testing; Time; Urine; Validation; X-Ray Computed Tomography; assay development; cancer type; detection sensitivity; diagnosis standard; evidence base; genetic profiling; liquid biopsy; preservation; prospective; radiological imaging; response; sample collection; serial imaging; standard of care; treatment response; tumor; tumor DNA; tumor progression; validation studies; viral DNA

Impact of pre-analytic procurement and processing variables on the detection of HCC DNA in urine Hepatocellular carcinoma (HCC) is the world’s 2nd leading cause of cancer-related death and one of the fastest-growing cancers in the US; 85% of patients die within 5 years, mainly due to late detection, limited treatment options, and high recurrence. Currently, HCC recurrence and treatment responses are monitored by serum AFP and serial imaging. Unfortunately, serum AFP can only be used for ~50% of HCC cases due to low sensitivity. While MRI/CT imaging is the gold standard for diagnosis, it is expensive and less accessible. It also has limited utility in the detection of small tumors (< 2 cm) and is challenging in the presence of dysplastic nodules. Early detection of recurrent HCC is ineffective with the current available methods. Genetic liquid biopsies have been routinely used in clinics for almost all cancer types as part of the National Comprehensive Cancer Network (NCCN) guideline. However, its usage in HCC is limited even though its promises have been well documented in the literature, mostly for blood and some for urine. Our hypothesis is that by establishing an evidence-based biospecimen practice for urine collection, storage, and transrenal DNA (trDNA) isolation, urine HCC DNA analysis with tailored sensitive assays can provide HCC genetics with more frequent tumor surveillance and treatment response assessment compared to current standard of care for prognosis. As a pioneer in developing urine cancer liquid biopsies, we have established the standard operating procedure (SOP) for urine collection for the Early Detection Research Network colon cancer validation study (protocol ID: 320) and other non-urinary tract cancers. We have identified pre-analytic variables that influence urine HCC DNA assay performance in the process of developing an HCC urine DNA test for HCC liquid biopsies. In this application, we propose to use a liver-specific trDNA marker, hepatitis B virus (HBV) DNA, which is found in urine, from patients with chronic HBV infection to validate and mitigate these pre-analytic variables. Aims 1 and 2, will identify, validate, and mitigate pre-analytic factors, associated with urine collection, storage and processing for trDNA isolation, and characterize of the size of trDNA that influences clinical assay results and reproducibility. As a result, an evidence-based urine biospecimen practice can be established to help support urine HCC DNA assay development, validation for HCC genetic liquid biopsy and assessment of treatment response. In Aim 3, we will then demonstrate the reproducibility and clinical validation of the utility of urine HCC DNA in assessing responses to HCC treatment. Developing a robust evidence-based urine biospecimen practice for sample collection, processing, and long-term storage will lead to the validation of urine tests for assessing HCC treatment in clinical trials.

预先分析的采购和加工变量对尿液中HCC DNA检测的影响 肝细胞癌（HCC）是世界上与癌症相关死亡的第二大主要原因，也是其中之一 在美国增长最快的癌症； 85％的患者在5年内死亡，主要是由于迟到，有限 治疗选择和高复发。目前，监测HCC复发和治疗反应 通过血清AFP和串行成像。不幸的是，血清AFP只能用于约50％的HCC病例 低灵敏度。尽管MRI/CT成像是诊断的黄金标准，但它很昂贵且易于使用。 它在检测小肿瘤（<2 cm）方面的效用也有限，并且在存在的情况下具有挑战性 发育不良结节。当前可用方法的早期检测反复检测无效。遗传 液体活检已在诊所中通常用于几乎所有癌症类型的诊所 综合癌症网络（NCCN）指南。但是，即使 文献中有充分的诺言已经有充分的文献记载，主要是关于血液的，有些是尿液。我们的假设 是通过建立基于证据的生物循环练习，以收集尿液，储存和跨性别 DNA（trDNA）分离，使用定制敏感测定的尿液HCC DNA分析可以提供HCC遗传学 与当前的护理标准相比，肿瘤监测和治疗反应评估更频繁 预后。作为发展尿液癌液体活检的先驱，我们已经建立了标准 早期检测研究网络结肠癌的尿液收集操作程序（SOP） 验证研究（协议ID：320）和其他非泌尿线癌。我们已经确定了预分析的 在开发HCC尿液DNA的过程中影响尿HCC DNA分析性能的变量 测试HCC液体活检。在此应用中，我们建议使用肝特异性TRDNA标记，乙型肝炎 在尿液中发现的病毒（HBV）DNA，来自慢性HBV感染的患者，以验证和减轻 这些预分析变量。 AIM 1和2将识别，验证和减轻近分析因素，相关的因素 尿液收集，储存和处理trDNA隔离，并以trdna的大小为特征 影响临床评估结果和可重复性。结果，基于证据的尿液生物测定 可以建立实践以帮助支持尿HCC DNA分析开发，验证HCC通用 液体活检和治疗反应的评估。在AIM 3中，我们将证明可重复性 以及尿HCC DNA在评估HCC治疗反应时的效用。发展 用于样品收集，处理和长期存储的强大基于证据的尿液生物测量实践 将导致在临床试验中评估HCC治疗的尿液测试验证。