Urine and serum biomarkers for early diagnosis and risk assessment of pancreatic cancer

用于胰腺癌早期诊断和风险评估的尿液和血清生物标志物

• 批准号: 10551280
• 负责人: Surinder K. Batra
• 金额: $ 62.24万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-02-03 至 2026-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10551280
• 关键词: Accounting; Algorithms; Benign; Biological Markers; Blinded; Body Fluids; Cancer Etiology; Cessation of life; Chinese; Classification; Clinical; Clinical Research; Cohort Studies; Communities; Curative Surgery; Data; Development; Diagnosis; Diagnostic; Differential Diagnosis; Discrimination; Disease; Early Diagnosis; Environment; Excision; Future; General Population; Genes; Goals; Health; Incidence; Individual; Institution; Intervention; Magnetic Resonance Imaging; Malignant Neoplasms; Malignant neoplasm of pancreas; Minority; Nurses' Health Study; Operative Surgical Procedures; Organ; Outcome; Pancreas; Pancreatic Adenocarcinoma; Pancreatic Ductal Adenocarcinoma; Pathology; Patient Care; Patients; Performance; Persons; Phase; Population; Probability; Prognosis; Prospective Studies; Prospective cohort; Prospective, cohort study; Proteins; Research; Resectable; Retrospective cohort; Risk; Risk Assessment; Sampling; Sensitivity and Specificity; Serum; Singapore; Site; Source; Specificity; Survival Rate; Symptoms; Testing; Training; Translations; Urine; Validation; Work; biomarker panel; candidate marker; care costs; clinical diagnosis; clinical translation; cohort; combinatorial; cost; early detection biomarkers; exosome; high risk; high risk population; improved; innovation; mortality; novel; novel diagnostics; patient subsets; prospective; protein biomarkers; screening; screening guidelines; specific biomarkers; surveillance strategy; tumor; urinary

ABSTRACT Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers, primarily due to most cases being diagnosed at an advanced, incurable stage. While 5-year survival of metastatic PDAC is <5%, outcomes dramatically improve for localized PDAC. Poor prognosis is due to a lack of biomarkers for diagnosing PDAC at an early, asymptomatic stage when cure is possible. Effective diagnosis of early stage PDAC depends on identification of accurate, non-invasive biomarkers in combination with a strategy for screening increased risk populations. Our primary objective is to identify non-invasive protein biomarkers in serum, urine, and exosomes that accurately distinguish between patients with and without early stage resectable PDAC that is amenable to curative surgery. Novel diagnostics would also improve discrimination between PDAC and benign pancreatic pathologies. The goal of the proposed research is to develop clinically translatable noninvasive biomarkers- based tests for screening (in high risk groups) and differential diagnosis of PDAC. Our central hypothesis is that combinations of urinary, serum, and exosome derived biomarkers could be synergistic offering a superior classification power. We have used urine and serum samples from retrospective and prospective cohort studies to identify a range of strong candidate combinatorial multimarker algorithms for early detection and diagnosis of PDAC. In Aim 1, we will optimize the performance of a PDAC differential diagnosis algorithm and will validate the optimized algorithm in samples collected prior to clinical diagnosis in the Pancreatic Adenocarcinoma Gene Environment Risk (PAGER) study. In Aim 2, we will optimize the performance of an early detection algorithm for resectable PDAC in pre-diagnostic samples from three prospectively collected cohorts and validate the optimized EDA in blinded parallel serum/urine samples from the Southern Community Cohort Study (SCCS). If successful, our project will yield novel, validated algorithms for risk assessment and early detection and for differential diagnosis of PDAC. These algorithms when combined will result in a new pioneering screening paradigm for PDAC allowing for timely live-saving interventions. Our strong preliminary data, powerful and synergistic investigative team, and the availability of parallel urine and serum samples from unique prospective cohorts contribute to the high probability of successful accomplishing the proposed studies.

抽象的 胰腺导管腺癌 (PDAC) 是最致命的癌症之一，主要是因为大多数病例 诊断时已处于晚期、无法治愈的阶段。虽然转移性 PDAC 的 5 年生存率 <5%，但结果 显着改善本地化 PDAC。预后不良是由于缺乏诊断 PDAC 的生物标志物 可以治愈的早期、无症状阶段。早期 PDAC 的有效诊断取决于 识别准确的、非侵入性的生物标志物，并结合筛查增加风险的策略 人口。我们的主要目标是鉴定血清、尿液和外泌体中的非侵入性蛋白质生物标志物 准确区分患有和不患有早期可切除 PDAC 的患者 治愈性手术。新颖的诊断方法还将改善 PDAC 和良性胰腺之间的区分 病理学。拟议研究的目标是开发临床可转化的非侵入性生物标志物 - 基于测试的 PDAC 筛查（高危人群）和鉴别诊断。我们的中心假设是 尿液、血清和外泌体衍生的生物标志物的组合可能具有协同作用，提供优越的结果 分类能力。我们使用了回顾性和前瞻性队列研究的尿液和血清样本 识别一系列强大的候选组合多标记算法，用于早期检测和诊断 PDAC。在目标 1 中，我们将优化 PDAC 鉴别诊断算法的性能并验证 胰腺癌基因临床诊断前收集样本的优化算法 环境风险（PAGER）研究。在目标 2 中，我们将优化早期检测算法的性能 在来自三个前瞻性收集的队列的诊断前样本中进行可切除的 PDAC 并验证优化后的结果 来自南方社区队列研究 (SCCS) 的盲法平行血清/尿液样本中的 EDA。如果成功的话， 我们的项目将产生新颖的、经过验证的算法，用于风险评估和早期检测以及差异化 PDAC 的诊断。这些算法结合起来将产生一种新的开创性筛选范例 PDAC 可以及时进行挽救生命的干预措施。我们强大的前期数据，强大且协同 研究团队，以及来自独特前瞻性队列的平行尿液和血清样本的可用性 有助于成功完成拟议研究的高可能性。