Core - Biomarker Reference Laboratory

项目总结/摘要（生物标志物参考实验室（BRL），RFA-CA-22-040） 我们建议开发一种基于血液的测试，其指示用途是在早期补充乳房X光检查。 检测乳腺癌。虽然乳房X光检查可以通过早期发现挽救生命，但它并不完美。 大约七分之一的乳腺癌在筛查性乳房X光检查中未被发现， 在正常乳房X光检查后一年内出现的癌症仍然是一个令人烦恼的问题，特别是（尽管不是） 专门）用于美国> 2700万具有不均匀或极致密乳房的女性， 患间歇性癌症的风险很高。我们建议开发一种血液测试，可以作为辅助手段， 乳腺X射线摄影术，以通过提高乳腺X射线摄影术的灵敏度和/或特异性来提高早期检测。 使用一种新的生物标志物发现方法，利用人鼠乳腺癌患者来源的 异种移植模型和最先进的质谱分析方法，我们优先考虑了162个候选者的子集 乳腺癌蛋白生物标志物（在乳腺癌病例与对照的人血浆中验证）用于随访 在本拟定BCC中进行的EDRN第2阶段验证研究。 我们的项目将在临床上验证和部署（在我们的CLIA实验室）一种新的多重免疫多重 进行EDRN 2期生物标志物的反应监测质谱（免疫-MRM-MS）测定 使用从现有生物储存库获得的强无偏血浆样品组进行验证研究。 生物标志物参考实验室将为拟议的EDRN第2阶段生物标志物验证做出贡献 （i）验证用于免疫MRM测定的符合CLIA的标准操作程序，以定量 多达162种早期乳腺癌的候选血浆蛋白质生物标志物，将作为我们研究的基础。 生物标志物验证研究，（ii）使用“强阳性”进行2期病例对照生物标志物验证研究， 使用EDRN PRoBE研究设计收集的“无偏倚”血浆样本，以及（iii）提供参考实验室 支持EDRN网络，包括高通量靶向质谱分析，流式细胞术， 下一代测序和96孔板ELISA测定。

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.