Evidence map›Paper›PMID 40826447›Full record

ArticleBMC cancer2025

Spatially resolved analysis of TGF/BMP signalling in pancreatic ductal adenocarcinoma by digital pathology identifies patient subgroups with adverse outcome.

Konstantin Bräutigam, Philipp Zens, Stefan Reinhard, Jessica L Rohrbach, Simon J Leedham, Anna S Wenning, Beat Gloor, Viktor H Koelzer, Martin Wartenberg

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Article in BMC cancer, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

9 authors.

Konstantin BräutigamCentre for Evolution and Cancer, Institute of Cancer Research, London, UK. konstantin.braeutigam@icr.ac.uk.
Philipp ZensInstitute of Tissue Medicine and Pathology, University of Bern, Bern, Switzerland.
Stefan ReinhardInstitute of Tissue Medicine and Pathology, University of Bern, Bern, Switzerland.
Jessica L RohrbachInstitute of Tissue Medicine and Pathology, University of Bern, Bern, Switzerland.
Simon J LeedhamIntestinal Stem Cell Biology Lab, Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK.
Anna S WenningDepartment of Visceral Surgery and Medicine, Inselspital Bern, Bern University Hospital, University of Bern, Bern, Switzerland.
Beat GloorDepartment of Visceral Surgery and Medicine, Inselspital Bern, Bern University Hospital, University of Bern, Bern, Switzerland.
Viktor H KoelzerDepartment of Pathology and Molecular Pathology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
Martin WartenbergInstitute of Tissue Medicine and Pathology, University of Bern, Bern, Switzerland.

Funding

Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung P2SKP3_168322/1Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung P500PM_217647/1
6 · The paper itself

Abstract

backgroundTransforming Growth Factor (TGF) and Bone Morphogenetic Protein (BMP) signalling critically influence pancreatic ductal adenocarcinoma (PDAC) progression, with TGF-B paradoxically exerting both tumour-promoting and -suppressive effects. Parallel to this observation, the specific context-dependent, spatial dynamics of these pathways and their interaction with the tumour microenvironment (TME) remain poorly understood.

methodsWe performed a spatially resolved analysis of PDAC on a multi-region tissue microarray cohort of 117 curatively resected PDAC specimens consisting of tumour centre (TC), tumour front (TF), and stromal(-predominant) tissue cores each. Protein (ID1, pSMAD2) and mRNA (TGF-A, TGF-B1/2, BMP4, GREM1) expression were assessed in each tissue compartment by immunohistochemistry and in situ hybridization, respectively, quantified by digital image analysis, and correlated with clinicopathologic features.

resultsID1 was significantly overexpressed in PDAC cells compared to associated stroma (p < 0.01), while pSMAD2 was largely absent in PDAC cells, but preserved among associated stroma compartments, particularly in TF cores (p = 0.04). Higher stromal GREM1 signal correlated with reduced overall tumoural ID1 protein expression (p = 0.02), and TGF-B2

conclusionsOur spatial analysis reveals intratumoural heterogeneity of TGF/BMP signalling and its significance for PDAC progression. Notably, stromal TGF-B2 emerges as a prognostic biomarker, while TGF-B1 and ID1 are implicated in adverse clinical and pathologic features. These findings highlight the importance of TGF/BMP signalling niches in the TME with implications for PDAC biology and can inform the development of future therapeutic strategies.

Indexed as

Bone Morphogenetic ProteinsCarcinoma, Pancreatic DuctalPancreatic NeoplasmsAdultAgedAged, 80 and overFemaleHumansImmunohistochemistryInhibitor of Differentiation Protein 1Intercellular Signaling Peptides and ProteinsMaleMiddle AgedPrognosisSignal TransductionSmad2 ProteinBone Morphogenetic ProteinsGREM1 protein, humanID1 protein, humanInhibitor of Differentiation Protein 1Intercellular Signaling Peptides and ProteinsSmad2 ProteinSMAD2 protein, humanAI (Artificial intelligence)Bone morphogenetic proteinsGREM1 proteinInhibitor of differentiation protein 1 (ID1)Pancreatic neoplasmsSpatial analysisStromal cellsTransforming growth factors

Identifiers

PMID40826447
PMCPMC12359875

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