Feasibility Study Utilizing NanoString’s Digital Spatial Profiling (DSP) Technology for Characterizing the Immune Microenvironment in Barrett’s Esophagus Formalin-Fixed Paraffin-Embedded Tissues

Author:

Qurat-ul-Ain 1ORCID,Frei Nicola F.2ORCID,Khoshiwal Amir M.2,Stougie Pim2,Odze Robert3,Camilleri-Broet Sophie4,Ferri Lorenzo4ORCID,Duits Lucas C.2,Bergman Jacques2,Stachler Matthew D.1ORCID

Affiliation:

1. Department of Pathology, University of California, San Francisco, CA 94143, USA

2. Amsterdam UMC Locatie AMC, 1105 AZ Amsterdam, The Netherlands

3. Department of Pathology, School of Medicine, Tufts University, Boston, MA 02111, USA

4. Division of Thoracic and Upper Gastrointestinal Surgery, Montreal General Hospital, McGill University, Montreal, QC H3G 1A4, Canada

Abstract

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.

Funder

American Cancer Society

National Institute of Health

Publisher

MDPI AG

Subject

Cancer Research,Oncology

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