Desmoplastic stromal signatures predict patient outcomes in pancreatic ductal adenocarcinoma.

Autor:	Mascharak S; Hagey Laboratory of Pediatric Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA., Guo JL; Hagey Laboratory of Pediatric Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA., Foster DS; Hagey Laboratory of Pediatric Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA., Khan A; Cell Sciences Imaging Facility, Stanford University, Stanford, CA 94305, USA., Davitt MF; Hagey Laboratory of Pediatric Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA., Nguyen AT; Hagey Laboratory of Pediatric Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA., Burcham AR; Hagey Laboratory of Pediatric Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA., Chinta MS; Hagey Laboratory of Pediatric Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA., Guardino NJ; Hagey Laboratory of Pediatric Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA., Griffin M; Hagey Laboratory of Pediatric Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA., Lopez DM; Hagey Laboratory of Pediatric Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA., Miller E; Department of Pathology, University of Virginia School of Medicine, Charlottesville, VA 22903, USA., Januszyk M; Hagey Laboratory of Pediatric Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA., Raghavan SS; Department of Pathology, University of Virginia School of Medicine, Charlottesville, VA 22903, USA., Longacre TA; Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA., Delitto DJ; Hagey Laboratory of Pediatric Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA., Norton JA; Hagey Laboratory of Pediatric Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA. Electronic address: janorton@stanford.edu., Longaker MT; Hagey Laboratory of Pediatric Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA. Electronic address: longaker@stanford.edu.
Jazyk:	angličtina
Zdroj:	Cell reports. Medicine [Cell Rep Med] 2023 Nov 21; Vol. 4 (11), pp. 101248. Date of Electronic Publication: 2023 Oct 20.
DOI:	10.1016/j.xcrm.2023.101248
Abstrakt:	Pancreatic ductal adenocarcinoma (PDAC) is projected to become the second leading cause of cancer-related death. Hallmarks include desmoplasia with variable extracellular matrix (ECM) architecture and a complex microenvironment with spatially defined tumor, stromal, and immune populations. Nevertheless, the role of desmoplastic spatial organization in patient/tumor variability remains underexplored, which we elucidate using two technologies. First, we quantify ECM patterning in 437 patients, revealing architectures associated with disease-free and overall survival. Second, we spatially profile the cellular milieu of 78 specimens using codetection by indexing, identifying an axis of pro-inflammatory cell interactions predictive of poorer outcomes. We discover that clinical characteristics, including neoadjuvant chemotherapy status, tumor stage, and ECM architecture, correlate with differential stromal-immune organization, including fibroblast subtypes with distinct niches. Lastly, we define unified signatures that predict survival with areas under the receiver operating characteristic curve (AUCs) of 0.872-0.903, differentiating survivorship by 655 days. Overall, our findings establish matrix ultrastructural and cellular organizations of fibrosis linked to poorer outcomes. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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