Urine based circulating tumor DNA analysis

基于尿液的循环肿瘤 DNA 分析

• 批准号: 10505548
• 负责人: Tim Lautenschlaeger
• 金额: $ 7.35万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 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/10505548
• 关键词: Biological Markers; Biological Models; Blood; Blood Cells; Cancer Patient; Chronic Kidney Failure; Clinical; DNA; DNA analysis; Data; Detection; Diagnosis; Disease; Excretory function; Gold; HPV oropharyngeal cancer; Home; Human Papillomavirus; Human papilloma virus infection; Iatrogenesis; Imaging Techniques; Kidney; Knowledge; Lead; Malignant Neoplasms; Malignant neoplasm of anus; Malignant neoplasm of cervix uteri; Methods; Molecular; Monitor; Newly Diagnosed; Nonmetastatic; Oncogenic; Parents; Patients; Physiological Processes; Radiation therapy; Recurrence; Sensitivity and Specificity; Source; Swab; Testing; Time; Tissues; Urine; base; biomarker performance; cell free DNA; cohort; in vivo fluorescence imaging; malignant oropharynx neoplasm; novel; performance tests; routine care; tumor DNA

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.

尿液是非泌尿生殖系统患者全身循环肿瘤 DNA 的一个未被充分认识的来源 癌症。根据最近的数据表明，基于血液的 HPV DNA 检测有助于疾病监测 在 HPV 阳性口咽癌患者中，我们发现了非转移性 HPV 阳性口咽癌 患者作为一个优秀的模型系统来检查基于尿液的经肾 DNA 分析的潜力。我们的 初步数据表明，我们新开发的基于尿液的 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，效果更佳。该应用程序的具体目标是确定 尿液是非转移性 HPV 阳性口咽癌患者 HPV DNA 的合适来源，并且 对于这些患者来说，在家进行基于尿液的分子检测是可行的。具体来说，我们将比较灵敏度 以及在一组新近治疗前基于尿液的 HPV 检测与组织金标准检测的特异性 诊断为非转移性口咽癌患者。尿液 HPV 复发检测周期 将在治疗性治疗后将测试与同一队列中的临床常规护理进行比较。控制将 包括基于血液的 HPV 检测、基于咽拭子的 HPV 检测和基于血液的个性化 ctDNA 测序面板测试。其他对照队列将包括宫颈癌和肛门癌患者以及 最近诊断出致癌 HPV 感染的无癌患者。使用体内荧光成像 技术，我们将获得有关无细胞 DNA 的肾脏处理的基础知识，并确定 慢性肾病和其他患者、疾病和医源性因素对细胞游离 DNA 排泄的影响。