부산대학교 도서관

Simple Summary: New biological insights into the stepwise development and progression of esophageal adenocarcinoma (EAC) from its pre-cancerous precursor, Barrett's esophagus (BE), are imperative to develop tailored approaches for the early detection and optimal clinical management of the disease. This study aimed to determine the feasibility of spatially profiling stromal and immunologic properties that accompany the malignant transformation of BE to EAC in standard clinical tissues. NanoString's GeoMx Digital Spatial Profiling (DSP) technology can detect and quantify protein and ribonucleic acid (RNA) transcripts in a highly multiplexed manner with spatial resolution. Here, we performed a pilot study using DSP, for the measurement of protein and RNA expression on a series of endoscopic samples of BE. We compare a small series of biopsies of non-dysplastic BE (NDBE) from patients who progressed to more advanced disease to patients with NBDE who did not progress, and then perform RNA profiling on samples with a range of histologic diagnoses. Characterization of the Barrett's esophagus (BE) microenvironment in patients with a known progression status, to determine how it may influence BE progression to esophageal adenocarcinoma (EAC), has been understudied, hindering both the biological understanding of the progression and the development of novel diagnostics and therapies. This study's aim was to determine if a highly multiplex interrogation of the microenvironment can be performed on endoscopic formalin-fixed, paraffin-embedded (FFPE) samples, utilizing the NanoString GeoMx digital spatial profiling (GeoMx DSP) platform and if it can begin to identify the types of immune cells and pathways that may mediate the progression of BE. We performed a spatial proteomic analysis of 49 proteins expressed in the microenvironment and epithelial cells of FFPE endoscopic biopsies from patients with non-dysplastic BE (NDBE) who later progressed to high-grade dysplasia or EAC (n = 7) or from patients who, after at least 5 years follow-up, did not (n = 8). We then performed an RNA analysis of 1812 cancer-related transcripts on three endoscopic mucosal resections containing regions of BE, dysplasia, and EAC. Profiling with GeoMx DSP showed reasonable quality metrics and detected expected differences between epithelium and stroma. Several proteins were found to have an increased expression within NDBE biopsies from progressors compared to non-progressors, suggesting further studies are warranted. [ABSTRACT FROM AUTHOR]