TY - JOUR
T1 - Feasibility Study Utilizing NanoString’s Digital Spatial Profiling (DSP) Technology for Characterizing the Immune Microenvironment in Barrett’s Esophagus Formalin-Fixed Paraffin-Embedded Tissues
AU - Qurat-ul-Ain, null
AU - Frei, Nicola F.
AU - Khoshiwal, Amir M.
AU - Stougie, Pim
AU - Odze, Robert
AU - Camilleri-Broet, Sophie
AU - Ferri, Lorenzo
AU - Duits, Lucas C.
AU - Bergman, Jacques
AU - Stachler, Matthew D.
N1 - Funding Information: This research was funded by the American Cancer Society Pilot Project award (MDS), NIDDK K08DK109209 (MDS), and NCI 1R37CA269649 (MDS). Publisher Copyright: © 2023 by the authors.
PY - 2023/12/1
Y1 - 2023/12/1
N2 - 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.
AB - 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.
KW - Barrett’s esophagus
KW - esophageal adenocarcinoma
KW - immune profiling
KW - spatial proteomics
KW - spatial transcriptomics
KW - tumor microenvironment
UR - http://www.scopus.com/inward/record.url?scp=85180695543&partnerID=8YFLogxK
U2 - https://doi.org/10.3390/cancers15245895
DO - https://doi.org/10.3390/cancers15245895
M3 - Article
C2 - 38136440
SN - 2072-6694
VL - 15
JO - Cancers
JF - Cancers
IS - 24
M1 - 5895
ER -