ArticleScientific reports2025
Analysis of an engineered organoid model of pancreatic cancer identifies hypoxia as a contributing factor in determining transcriptional subtypes.
Article in Scientific reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 3 papers.
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Who cites it
3 citing papers in PubMed.
- Bioengineering advances in pancreatic cancer organoids for reproducible tumor microenvironment modeling.iScience · 2026Review
- Early cellular plasticity promotes progression and dissemination in pancreatic adenocarcinoma.Cancer metastasis reviews · 2026Review
- Organoids for disease modeling and treatment: state-of-the-art.Experimental hematology & oncology · 2026Review
Corrections and comments
- Erratum issued
Authors and funding
13 authors.
Funding
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is a high-mortality cancer characterized by its aggressive, treatment-resistant phenotype and a complex tumour microenvironment (TME) featuring significant hypoxia. Bulk transcriptomic analysis has identified the "classical" and "basal-like" transcriptional subtypes which have prognostic value; however, it is not well-established how microenvironmental heterogeneity contributes to these transcriptional signatures. Here, we exploited the TRACER platform to perform single cell transcriptome analysis of organoids at specific spatial locations to explore the effect of oxygen and other cell-generated microenvironmental gradients on organoid heterogeneity. We found that the microenvironmental gradients present in TRACER significantly impact the distribution of organoid transcriptional phenotypes and the enrichment of gene sets linked to cancer progression and treatment resistance. More significantly, we found that microenvironmental gradients, predominantly oxygen, drive changes in the expression of classical and basal-like transcriptional subtype gene signatures. This work suggests that hypoxia contributes to determining transcriptional subtypes in PDAC tumour cells independent of additional cells in the TME and broadly highlights the importance of considering microenvironmental gradients such as oxygen in organoid-based studies.
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