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Urine based circulating tumor DNA analysis

基于尿液的循环肿瘤 DNA 分析

基本信息

批准号：
10653030
负责人：
Tim Lautenschlaeger
金额：
$ 44.62万
依托单位：
INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-07-01 至 2026-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10653030
关键词：
Anus Bilateral Biological Markers Biological Models Blood Blood Cells Blood Volume Body mass index Cancer Control Cancer Patient Chronic Kidney Failure Clinical Collection DNA DNA analysis DNA sequencing Data Detection Diagnosis Disease Eligibility Determination Excretory function Filtration Future Gender Gene Frequency Genital Genitalia Genome Goals HPV analysis HPV oropharyngeal cancer Head Cancer Home Hour Human Papilloma Virus Vaccination Human Papilloma Virus-Related Malignant Neoplasm Human Papillomavirus Human papilloma virus infection Iatrogenesis Imaging Techniques Incidence Kidney Kidney Diseases Kinetics Knowledge Lead Longitudinal Studies Malignant Neoplasms Malignant neoplasm of anus Malignant neoplasm of cervix uteri Methodology Modeling Molecular Monitor Mutation Mutation Detection Nature Neck Cancer Nephrectomy Newly Diagnosed Nonmetastatic Oncogenic Organ Outcome Patients Performance Persons Pharmaceutical Preparations Pharyngeal structure Physiological Processes Pilot Projects Plasma Radiation Dose Unit Radiation therapy Rattus Recurrence Research Screening for cancer Sensitivity and Specificity Source Stream Swab Testing Time Tissues Tube Urine Validation biomarker performance blood fractionation cell free DNA cohort detection sensitivity improved in vivo Model in vivo fluorescence imaging interest liquid biopsy malignant oropharynx neoplasm men novel performance tests pharyngeal swab routine care single molecule targeted treatment tumor DNA

项目摘要

ABSTRACT Urine is an underappreciated source for systemic circulating tumor DNA in patients with non-genitourinary cancers. Based on recent data suggesting that blood-based HPV DNA testing is useful for disease monitoring in HPV positive oropharynx cancer patients, we identified non-metastatic HPV positive oropharyngeal cancer patients as an excellent model system to examine the potential of urine-based transrenal DNA analysis. Our preliminary data suggests that our newly developed urine-based HPV test could have biomarker performances comparing favorably to blood-based HPV testing. The specific objectives of this application are to establish that urine is a suitable source for HPV DNA in non- metastatic HPV positive oropharynx cancer patients, and that at-home urine based molecular testing is feasible for these patients. Specifically, we will compare sensitivity and specificity of pre-therapy urine-based HPV testing to tissue gold standard testing in a cohort of newly diagnosed non-metastatic oropharyngeal cancer patients. Recurrence detection lead time of urine-based HPV testing will be compared to clinical routine care in the same cohort after curative intent treatment. Controls will include blood-based HPV testing, pharyngeal swab-based HPV testing and blood based personalized ctDNA sequencing panel testing. Additional control cohorts will include cervical and anal cancer patients as well as cancer-free patients with recently diagnosed oncogenic HPV infections. Using in vivo fluorescence imaging techniques, we will generate fundamental knowledge on renal handling of cell free DNA and determine the impact of chronic kidney disease and other patient, disease and iatrogenic factors on cell free DNA excretion.

摘要尿液是非泌尿生殖道肿瘤患者全身循环肿瘤DNA的一个未被充分认识的来源癌的基于最近的数据表明，基于血液的HPV DNA检测对疾病监测是有用的在HPV阳性的口咽癌患者中，我们发现非转移性HPV阳性的口咽癌患者作为一个很好的模型系统，以检查基于尿液的跨肾DNA分析的潜力。我们初步数据表明，我们新开发的尿液HPV检测可能具有生物标志物性能，与基于血液的HPV检测相比，本申请的具体目的是确定尿液是非HPV感染中HPV DNA的合适来源。转移性HPV阳性口咽癌患者，在家尿液分子检测是可行的对于这些患者。具体来说，我们将比较治疗前尿中HPV检测的敏感性和特异性。在新诊断的非转移性口咽癌队列中进行组织金标准检测患者基于尿液的HPV检测的复发检测提前时间将与临床常规护理进行比较，同一队列接受根治性治疗后。控制将包括基于血液的HPV检测，咽部基于拭子的HPV检测和基于血液的个性化ctDNA测序面板检测。附加控制队列将包括宫颈癌和肛门癌患者以及最近诊断为致癌性HPV感染。使用体内荧光成像技术，我们将产生基本的了解肾脏处理细胞游离DNA的知识，并确定慢性肾脏疾病和其他疾病的影响患者、疾病和医源性因素对细胞游离DNA排泄的影响。