Spatial transcriptome profiling of pancreatic cancer identifies multicellular dynamics associated with neoadjuvant treatment
Dataset ID: STDS0000150
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PMID:35928007
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Summary:
Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal and treatment-refractory cancer. Molecular stratification in pancreatic cancer remains rudimentary and does not yet inform clinical management or therapeutic development. Here we construct a high-resolution molecular landscape of the multicellular subtypes and spatial communities that compose PAC using single-nucleus RNA-seq and whole-transcriptome digital spatial profiling (SP) of 43 primary PDAC tumor specimens that either received neoadjuvant therapy or were treatment-naïve. We uncovered expression programs across malignant cells and fibroblasts, including a newly-identified neural-like progenitor malignant cell program that was enriched after chemotherapy and radiotherapy and associated with poor prognosis in independent cohorts. Integrating spatial and cellular profiles revealed three multicellular communities: classical, squamoid-basaloid, and treatment-enriched. Our refined molecular and cellular taxonomy can advance precision oncology in PAC through stratification in clinical trials and as roadmap for therapeutic targeting of specific cellular phenotypes and multicellular interactions.
Overall design:
14 specimens received no treatment prior to resection; 7 specimens received neoadjuvant chemotherapy, radiotherapy, losartan, and/or nivolumab prior to resection
Technology:
GeoMx DSP
Platform:
Illumina NovaSeq 6000 (Homo sapiens)
Species:
Homo sapiens
Tissues:
Pancreas
Disease:
Pancreatic ductal adenocarcinoma
Citation:
Whitsitt, Quentin A et al. “Spatial Transcriptomics as a Novel Approach to Redefine Electrical Stimulation Safety.” Frontiers in neuroscience vol. 16 937923. 19 Jul. 2022, doi:10.3389/fnins.2022.937923
Submission date: 2022-03-21Update date: 2022-05-13
Sample number: 608
Contributors
Hwang, William L; Jagadeesh, Karthik A; Guo, Jimmy A; Hoffman, Hannah I; Su, Jennifer; Shiau, Carina; Jacks, Tyler; Regev, Aviv
Accessions
GEO Series Accessions: GSE199102