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: 10339431
• 负责人: Surinder K. Batra
• 金额: $ 62.64万
• 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/10339431
• 关键词: Accounting; Address; Algorithms; Benign; Biological Markers; Blinded; 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; Liquid substance; 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; Research; Resectable; Retrospective cohort; Risk; Risk Assessment; Sampling; Savings; Sensitivity and Specificity; Serum; Serum Proteins; Singapore; Site; Source; Specificity; Survival Rate; Symptoms; Testing; Time; Training; Translations; Urine; Validation; Work; base; biomarker panel; candidate marker; care costs; clinical diagnosis; clinically translatable; 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，主要是由于大多数情况是 在高级，无法治愈的阶段进行诊断。虽然转移性PDAC的5年生存率<5％，结果 局部PDAC大大改进。预后不良是由于缺乏诊断PDAC的生物标志物所致 可以治愈的早期，无症状的阶段。有效诊断早期PDAC取决于 确定准确的非侵入性生物标志物与筛查策略的结合增加风险 人群。我们的主要目的是鉴定血清，尿液和外泌体中的非侵入性蛋白质生物标志物 这可以准确区分有和没有早期可切除PDAC的患者，这很适合 治疗手术。新颖的诊断还将改善PDAC和良性胰腺的歧视 病理。拟议研究的目的是开发可翻译的非侵入性生物标志物 - 基于筛查的测试（在高风险组中）和PDAC的差异诊断。我们的中心假设是 尿，血清和外泌体衍生的生物标志物的组合可能是协同的，可以提供优质 分类功率。我们使用了回顾性和前瞻性队列研究中的尿液和血清样品 确定一系列强大的候选组合多标志物算法，用于早期检测和诊断 PDAC。在AIM 1中，我们将优化PDAC差异诊断算法的性能，并将验证 胰腺腺癌基因临床诊断之前收集的样品中的优化算法 环境风险（PAGER）研究。在AIM 2中，我们将优化早期检测算法的性能 来自三个前瞻性收集的队列的诊断前样品中可切除的PDAC，并验证了优化的 来自南部社区队列研究（SCC）的盲平行血清/尿液样品中的EDA。如果成功， 我们的项目将产生新颖的，经过验证的算法，以进行风险评估和早期检测以及差异 诊断PDAC。这些算法合并后将导致新的开拓性筛选范式 PDAC允许及时挽救生存干预措施。我们强大的初步数据，强大而协同的 调查团队，以及来自独特前瞻性队列的平行尿液和血清样品的可用性 有助于成功完成所提出的研究的高可能性。