PO.CL01.18 · 临床研究

使用新型集成nCounter®工作流程在单张FFPE组织切片上快速鉴定全面的多组学蛋白质和RNA生物标志物

Rapid identification of comprehensive multi-omic protein and RNA biomarkers on a single FFPE tissue section using a novel integrated nCounter® workflow

海报缩略图:使用新型集成nCounter®工作流程在单张FFPE组织切片上快速鉴定全面的多组学蛋白质和RNA生物标志物
编号 1106 展板 16 时间 4/19 02:00–05:00 区域 Section 43 主讲 Lakshmi Chandramohan, PhD
分会场 Early Detection Biomarkers 1
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作者与单位 Authors & Affiliations

Lakshmi Chandramohan1, Kirsteen Maclean1, Quratul Ain1, Brigitte Lovell1, Lisa Duncan1, Sergio Hernandez1, Christina Bailey2, Michael Bailey2, Patrick Danaher2, Wei Yang2, Shanshen He2, Joseph M. Beechem2

1NeoGenomics, Fort Myers, FL,2Bruker Spatial Biology, Bothell, WA

摘要 Abstract

中文摘要
背景:能够从同一组织切片快速鉴定和定量转录组和蛋白质组数据集的生物标志物检测方法,对于研究肿瘤高度复杂的生物学变得日益宝贵。遗憾的是,如今在诸如FFPE切片上对蛋白质和RNA进行真正多组学分析的主要挑战在于福尔马林固定和储存导致的分子降解和交联,从而产生质量不稳定且低下的核酸和蛋白质。这种降解,加之样本固有的异质性,使得难以提取高产量的分子,并需要复杂的生物信息学方法来整合由此产生的复杂且往往充满噪声的多组学数据。为满足这一需求,我们开发并验证了一种使用nCounter®分析系统的新型工作流程,能够从同一张切片同时定量mRNA和蛋白质靶标。这种"多组学变简单"的方法由Bruker Spatial Biology的精简工作流程和直接杂交化学独特实现,现已通过NeoGenomics提供并验证。 方法:该工作流程的核心创新在于其能够从单张FFPE切片测量mRNA和蛋白质信号,作为简单三步流程的一部分。具体而言,该检测利用了传统nCounter mRNA面板(如可测量多达800个基因表达靶标的PanCancer IO 360™面板)与新设计和优化的蛋白质面板(能够在统一流程中分析多达800种蛋白质)的协调整合。为验证性能规范,领先的临床研究组织NeoGenomics在多种FFPE样本类型(包括乳腺、肺、结直肠、膀胱和尿路上皮肿瘤)中评估了这一多组学应用。 结果:在所有组织类型中,该精简检测展现出高特异性、重复运行间的强相关性以及mRNA和蛋白质分析物均具有出色的动态范围。这些结果证实了该平台在广泛肿瘤生物学背景下的实用性,并支持其用于生物标志物发现、靶点验证和作用机制研究。通过从单张组织切片提供mRNA和蛋白质的联合分析,nCounter平台能够快速鉴定肿瘤特异性特征,加强生物学解读并简化转化工作流程的复杂性。 结论:这一新近验证的应用现已通过NeoGenomics提供,使研究团队能够通过简单、可扩展和可重复的工作流程释放真正组织多组学的协同力量——使从FFPE组织进行同一切片mRNA+蛋白质分析成为制药和转化研究的实际现实。
查看英文原文 English abstract
Background: Biomarker detection approaches capable of rapid identification and quantification of both transcriptomic and proteomic datasets from the same tissue section have become increasingly valuable for investigating the highly complex biology of tumors. Unfortunately, today, the main challenges of true multi-omic analysis of protein and RNA on e.g. FFPE slides are the degradation and cross-linking of molecules from formalin fixation and storage, leading to variable and low-quality nucleic acids and proteins. This degradation, combined with inherent sample heterogeneity, makes it difficult to extract high yields of molecules and requires sophisticated bioinformatic methods to integrate resulting complex and often noisy multi-omics data. To address this need, we have developed and validated a novel workflow using the nCounter® Analysis System that enables simultaneous quantification of mRNA and protein targets from the same slide. This ‘multiomics made simple' approach is uniquely enabled by Bruker Spatial Biology's streamlined workflow and direct hybridization chemistry, now accessible and validated through NeoGenomics. Methods: The core innovation of this workflow lies in its ability to measure both mRNA and protein signal from a single FFPE slide as part of a simple 3-step protocol. Specifically, the assay leverages the harmonization of traditional nCounter mRNA Panels such as the PanCancer IO 360™ panel that measures up to 800 gene expression targets alongside newly designed and optimized Protein Panels capable of analyzing up to 800 proteins within a unified protocol. To validate performance specifications, NeoGenomics, a leading clinical research organization, evaluated this multi-omics application across diverse FFPE sample types, including breast, lung, colorectal, bladder, and urothelial tumors. Results: Across all tissue types, the streamlined assay demonstrated high specificity, strong correlation between replicate runs, and excellent dynamic range for both mRNA and protein analytes. These results confirm the platform's utility across a wide range of tumor biology contexts and support its adoption for biomarker discovery, target validation, and mechanism-of-action studies. By delivering combined mRNA and protein profiling from a single tissue section, the nCounter platform enables rapid identification of tumor-specific signatures, strengthening biological interpretation and simplifying translational workflow complexity. Conclusions: This newly validated application, now available through NeoGenomics, empowers research teams to unlock the synergistic power of true tissue multiomics through a simple, scalable, and reproducible workflow-making same-slide mRNA+Protein analysis from FFPE tissue a practical reality for pharma and translational research.
利益披露 Disclosure
L. Chandramohan, None.. K. Maclean, None.. Q. Ain, None.. B. Lovell, None.. L. Duncan, None.. S. Hernandez, None.. C. Bailey, None.. M. Bailey, None.. P. Danaher, None.. W. Yang, None.. S. He, None.. J. M. Beechem, None.

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