Abstract

Abstract Although many new drugs have been approved and more clinical trials are being conducted for various disease therapies in recent decades, efficient identification of reliable therapeutic targets is still a big challenge during drug development. Therefore, tremendous efforts have been put into advancing the technology to quickly determine the altered biomarkers in clinical samples. Nanostring nCounter GeoMxTM Digital Spatial Profiling (GeoMx DSP) has been used in multiple projects and exhibited its outstanding performance on collecting analyzable digital counts for up-to 96 proteins and 20,000 RNAs in a specific area on a single FFPE slide. Tissue regions of interests are identified by fluorescent staining of morphology markers, and either proteins or RNAs in the specific defined regions are collected as the digital nCounter count format. By using this state-of-art technology, spatial distributions of immune- and cancer- relevant proteins were identified in 71 tumor cell rich-, 70 immune cell rich-, and 69 stromal cell rich- area respectively in three Pancreatic cancer patient groups including surgery alone, neoadjuvant FOLFIRINOX (a combination of fluorouracil, folinic acid, irinotecan and oxaliplatin) alone or combined with stereotactic body radiation therapy (F+SBRT). Our results showed that differential regulations among immune checkpoint markers, pan-immune markers and tumor markers in these treatment groups. In tumor-rich regions, CD44 is present at higher levels in FOLFIRINOX treated patients than surgery-alone group. VISTA was significantly down-regulated in F+SBRT group. Also, several key factors from pStat3, PTEN and Bcl2 pathways are also regulated by treatment methods. In immune-rich regions, both T cells markers (CD3 and CD4) and B cell markers (CD19 and CD20) were regulated differently by treatment methods. GeoMx DSP platform provides a novel and more precise view of the spatial regulation of micro-world in the tissue, which enable us to explore more about internal regulation within sub-population of the tissue cells. GeoMxTM DSP platform is only for RESEARCH USE ONLY. Not for use in diagnostic procedures. Citation Format: Jingjing Gong, Matthew R. Farren, Walid Shaib, Gregory Lesinski, Sarah Warren, Yan Liang. Small slide, big world: Fast detection of altered proteins and RNA levels in clinical samples using Nanostring nCounter® GeoMxTM Digital Spatial Profiler [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 6499.

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