Biomarker Reference Lab

生物标志物参考实验室

• 批准号: 10701257
• 负责人: Leopoldo Nicolas Segal
• 金额: $ 10.24万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-05-04 至 2028-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10701257
• 关键词: Adjuvant; Benign; Biological Assay; Biological Markers; Blood; Blood specimen; Cancer Patient; Clinical; Clinical Laboratory Improvement Amendments; Collaborations; Cost efficiency; Custom; DNA; DNA Probes; Data; Detection; Development; Diagnosis; Diagnostic; Disease; Early Detection Research Network; Early identification; Evaluation; Excision; Freezing; Genes; Genome; Goals; Infrastructure; Intervention; Investigation; Laboratories; Malignant Neoplasms; Malignant neoplasm of lung; Measures; Metagenomics; Nature; Neoadjuvant Therapy; Non-Small-Cell Lung Carcinoma; Patients; Plasma; Procedures; Prognosis; RNA; Recurrence; Recurrent Malignant Neoplasm; Reproducibility; Role; Sampling; Standardization; Sterility; Structure of parenchyma of lung; Testing; Tissue Sample; Tissues; Validation; Work; biomarker development; biomarker validation; cancer diagnosis; cancer recurrence; cohort; design; diagnostic strategy; experience; genomic signature; high risk; metabolome; metagenome; microbial; microbial genomics; microbial signature; microbiome; nano-string; next generation sequencing; novel; novel strategies; predictive signature; prevent; prognostic; risk prediction; sequencing platform; targeted sequencing; transcriptome

Project summary (BRL) The ultimate goal of the NYU BCC EDRN is to develop Clinical Laboratory Improvement Amendments (CLIA) grade assays that will allow for identification of early stage lung cancer and will predict the risk of recurrence post-surgical removal of early stage disease. We already have promising data that this can be accomplished through evaluation of microbial and host genomic signatures. These will be further investigated in the Biomarker Developmental Laboratory (BDL) with agnostic omics approaches leading to identification of best performing predictive features. The goal of the Biomarker Reference Laboratory (BRL) is to develop standardized, analytically validated-biomarker assays that will target promising microbial and host signatures identified by the BDL. In order to do so, we will have matching plasmas, buffy coats, and lower airway samples to the ones used in the BDL for discovery as reference samples for “first order” clinical validation of our custom panels in the BRL. In Aim 1, we will develop a targeted microbial genomic next generation sequencing (NGS) panel for blood and lower airway samples predictive of diagnosis and prognosis of early-stage NSCLC. DNA probes will be designed targeting taxa identified in the BDL. In Aim 2, we will evaluate whether a targeted metabolite panel using an LC- MS approach in blood and lower airway samples can predict diagnosis and prognosis of early-stage NSCLC. In Aim 3, we will test a custom-made NanoString panel for RNA from buffy coats and lower airways targeting best performing features identified in the BDL. The cohort selected will be divided in Discovery and Validation. Successful biomarkers will then undergo external validation. The proposed work will be performed in our CLIA approved laboratory infrastructure. The pipelines developed here will provide a novel approach that can be customized to multiple targets identified by others in the EDRN consortium. While each approach is distinctly looking at microbial DNA, metabolites or host RNA target signatures, the consistent use of samples from a defined group of subjects will allow us to estimate the role of combining different types of biomarkers measured in parallel through different approaches for diagnostic and prognostic prediction. These investigations can then lead to the development of a new multi-approach biomarker that will identify high risk subjects where more aggressive interventions might be warranted.

项目摘要（巴西雷亚尔） 纽约大学BCC EDRN的最终目标是制定临床实验室改进修正案（CLIA） 允许识别早期肺癌并预测复发风险的分级检测 早期疾病的术后切除。我们已经有很有希望的数据表明这是可以实现的 通过评估微生物和宿主基因组特征。这些将在生物标志物中进一步研究 发展实验室（BDL）与不可知组学方法，导致识别最佳性能 预测功能。生物标志物参考实验室（BRL）的目标是开发标准化， 分析验证的生物标志物检测，将针对由 BDL。为了做到这一点，我们将有匹配的血浆，血沉棕黄层，和下呼吸道样本的使用 在BDL中作为参考样本用于BRL中我们定制样本组的“一级”临床验证。 在目标1中，我们将开发一种针对血液和组织的靶向微生物基因组下一代测序（NGS）面板。 下呼吸道样本可预测早期NSCLC的诊断和预后。将设计DNA探针 以BDL中鉴定的分类群为目标。在目标2中，我们将评估是否使用LC-100靶向代谢物组。 血液和下呼吸道标本中的MS方法可以预测早期NSCLC的诊断和预后。在 目标3，我们将测试一个定制的NanoString面板，用于从血沉棕黄层和下呼吸道最佳靶向的RNA 执行BDL中标识的特征。选定的队列将分为发现和验证。 成功的生物标志物将接受外部验证。拟议的工作将在我们的CLIA中进行 实验室基础设施。这里开发的管道将提供一种新颖的方法， 根据EDRN联盟中其他人确定的多个目标进行定制。虽然每一种方法都是不同的， 通过观察微生物DNA、代谢物或宿主RNA靶标特征， 一组确定的受试者将使我们能够估计结合不同类型的生物标志物测量的作用 并行通过不同的方法进行诊断和预后预测。这些调查可以 导致开发一种新的多方法生物标志物，将识别高风险受试者， 可能需要采取积极的干预措施。