Core - Biomarker Reference Laboratory

核心 - 生物标志物参考实验室

基本信息

批准号：
10701483
负责人：
ANDREW N HOOFNAGLE
金额：
$ 4万
依托单位：
FRED HUTCHINSON CANCER CENTER
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-06-05 至 2028-05-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10701483
关键词：
Area Benign Biological Assay Biological Markers Biopsy Blinded Blood Blood Tests Blood specimen Breast Breast Cancer Early Detection Breast Diseases Breast biopsy CLIA certified Characteristics Clinical Clinical Chemistry Collaborations Collection Complement Development Digestion ERBB2 gene Early Detection Research Network Early Diagnosis Environment Enzyme-Linked Immunosorbent Assay Evaluation Evaluation Studies Flow Cytometry Goals Guidelines Human Laboratories Malignant Neoplasms Mammary Neoplasms Mammographic screening Mammography Mass Spectrum Analysis Medicine Methods Mus Pathologic Patient Selection Patient-derived xenograft models of breast cancer Patients Phase Plasma Plasma Proteins Preparation Procedures Proteins Qualifying Quality Control Reagent Regulation Reproducibility Research Design Sampling Selection Bias Services Specificity Target Populations Technology Testing Thyroglobulin Translating United States Validation Variant Woman biobank biomarker discovery biomarker validation cancer biomarkers cancer invasiveness candidate marker case control early detection biomarkers experience follow-up high risk improved instrumentation malignant breast neoplasm manufacturing run multiple reaction monitoring multiplex assay next generation sequencing novel novel marker pre-clinical prospective protein biomarkers quality assurance repository sample collection support network validation studies

项目摘要

Project Summary/Abstract (Biomarker Reference Laboratory (BRL), RFA-CA-22-040) We propose to develop a blood-based test whose indicated use is to complement mammography in the early detection of breast cancers. Although mammography saves lives through early detection, it is imperfect. Approximately one in seven breast cancers goes undetected despite screening mammography, and interval cancers that manifest within a year of a normal mammogram remain a vexing problem, especially (although not exclusively) for the >27 million women in the United States with heterogeneously or extremely dense breasts at high risk for interval cancers. We propose to develop a blood test that could be used as an adjunct to mammography to improve early detection by improving sensitivity and/or specificity of mammography. Using a novel biomarker discovery approach leveraging human-in-mouse breast cancer patient-derived xenograft models and state-of-the-art mass spectrometry methods, we prioritized a subset of 162 candidate breast cancer protein biomarkers (verified in human plasma from breast cancer cases vs. controls) for follow up EDRN phase 2 validation studies in this proposed BCC. Our project will clinically validate and deploy (in our CLIA laboratories) a novel multiplex immuno-multiple reaction monitoring mass spectrometry (immuno-MRM-MS) assay to perform EDRN phase 2 biomarker validation studies using strongly unbiased sets of plasma samples obtained from existing biorepositories. The Biomarker Reference Laboratory will contribute to the proposed EDRN phase 2 biomarker validation studies by: (i) validating a CLIA-compliant standard operating procedure for an immuno-MRM assay to quantify up to 162 candidate plasma protein biomarkers of early-stage breast cancer that will serve as the basis for our biomarker validation studies, (ii) performing a phase 2 case-control biomarker validation study using “strongly unbiased” plasma collections collected using EDRN PRoBE study design, and (iii) providing reference laboratory support for the EDRN network, including high-throughput targeted mass spectrometric analyses, flow cytometry, next-gen sequencing, and 96-well plate ELISA assays, as needed.

项目摘要/摘要（生物标志物参考实验室（BRL），RFA-CA-22-040）我们建议开发基于血液的测试，其指示的用途是在早期完成乳房X线摄影尽管乳房X线摄影通过早期发现可以挽救生命，但这是不完美的。大约有七分之一的乳腺癌进行了未发现的目的地筛查乳房摄影和间隔在正常乳房X线照片后一年内表现出的癌症仍然是一个烦人的问题，尤其是独家）对于美国的2700万妇女，乳房异质性或非常密集的乳房间隔癌的高风险。我们建议开发一种可以用作辅助的血液检查通过提高乳房X线摄影的敏感性和/或特异性来改善乳房X线摄影以改善早期检测。使用一种新型的生物标志物发现方法利用人类室内乳腺癌患者衍生主体模型和最先进的质谱法，我们优先考虑162个候选人的子集乳腺癌蛋白生物标志物（乳腺癌病例与对照组中的人血浆验证）可随访 EDRN第2阶段验证研究中的该拟议的BCC。我们的项目将在临床上验证和部署（在我们的CLIA实验室），这是一个新颖的多次免疫媒体。反应监测质谱法（Immuno-MRM-MS）测定以执行EDRN阶段2生物标志物使用从现有的生物塑料中获得的强烈无偏血浆样品集的验证研究。生物标志物参考实验室将有助于拟议的EDRN阶段2生物标志物验证研究作者：（i）验证符合CLIA符合免疫MRM测定的标准标准操作程序以量化早期乳腺癌的162个候选血浆蛋白生物标志物将作为我们的基础生物标志物验证研究，（ii）使用“强烈的使用EDRN探针研究设计收集的无偏血浆收集，（iii）提供参考实验室支持EDRN网络，包括高通量目标质谱分析，流式细胞仪，根据需要，下一代测序和96孔板ELISA分析。