Evidence map›Paper›PMID 42632864›Full record

ArticleBritish journal of cancer2026

Dual-oxygen pancreatic cancer organoids recapitulate basal-classical heterogeneity validated by spatial transcriptomics.

Koichiro Kumano, Hiromitsu Nakahashi, Osamu Shimomura, Yoshimasa Akashi, Yoshihiro Miyazaki, Yohei Owada, Shinji Hashimoto, Kazuto Kamohara, Shuhei Komatsuzaki, Yukihito Kuroda and 10 more

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Article in British journal of cancer, 2026. 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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2 · The registry

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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

20 authors.

Koichiro Kumano *Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Institute of Medicine, University of Tsukuba, Tsukuba, Japan.ORCID http://orcid.org/0000-0001-8032-167X
Hiromitsu Nakahashi *Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Institute of Medicine, University of Tsukuba, Tsukuba, Japan.
Osamu ShimomuraDepartment of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Institute of Medicine, University of Tsukuba, Tsukuba, Japan.
Yoshimasa AkashiDepartment of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Institute of Medicine, University of Tsukuba, Tsukuba, Japan.
Yoshihiro MiyazakiDepartment of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Institute of Medicine, University of Tsukuba, Tsukuba, Japan.
Yohei OwadaDepartment of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Institute of Medicine, University of Tsukuba, Tsukuba, Japan.
Shinji HashimotoDepartment of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Institute of Medicine, University of Tsukuba, Tsukuba, Japan.
Kazuto KamoharaDepartment of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Institute of Medicine, University of Tsukuba, Tsukuba, Japan.
Shuhei KomatsuzakiDepartment of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Institute of Medicine, University of Tsukuba, Tsukuba, Japan.
Yukihito KurodaDepartment of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Institute of Medicine, University of Tsukuba, Tsukuba, Japan.
Jaejeong KimDepartment of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Institute of Medicine, University of Tsukuba, Tsukuba, Japan.
Pakavarin LouphrasitthipholDepartment of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Institute of Medicine, University of Tsukuba, Tsukuba, Japan.
Colin R GodingNuffield Department of Medicine, Ludwig Institute for Cancer Research, University of Oxford, Oxford, UK.
Yoshiaki AbeDepartment of Hematology, Institute of Medicine, University of Tsukuba, Tsukuba, Japan.ORCID http://orcid.org/0000-0002-1021-7911
Mamiko Sakata-YanagimotoDepartment of Hematology, Institute of Medicine, University of Tsukuba, Tsukuba, Japan.
Noriaki SakamotoDepartment of Pathology, Institute of Medicine, University of Tsukuba, Tsukuba, Japan.
Daisuke MatsubaraDepartment of Pathology, Institute of Medicine, University of Tsukuba, Tsukuba, Japan.
Ayako SuzukiDepartment of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Chiba, Japan.
Yutaka SuzukiDepartment of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Chiba, Japan.
Tatsuya OdaDepartment of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Institute of Medicine, University of Tsukuba, Tsukuba, Japan. tatoda@md.tsukuba.ac.jp.ORCID http://orcid.org/0000-0001-6115-0158

Funding

MEXT | Japan Society for the Promotion of Science (JSPS) 22H02911MEXT | Japan Society for the Promotion of Science (JSPS) 22K16504MEXT | Japan Society for the Promotion of Science (JSPS) 23K19527
6 · The paper itself

Abstract

backgroundPancreatic ductal adenocarcinoma (PDAC) comprises heterogeneous classical and basal-like subtypes. Although pancreatic cancer organoids (PCOs) are widely used, normoxic cultures preferentially maintain the classical subtype, limiting their ability to represent intrinsic intratumoral heterogeneity. Because PDAC develops in profoundly hypoxic microenvironments, the influence of oxygen tension on organoid modelling remains unclear.

methodsWe performed spatially resolved single-cell transcriptomics on 12 primary PDAC tumours to map the distributions of classical and basal-like cells. Paired organoids were generated under normoxic (20% O₂; NORM-PCOs) and hypoxic (1% O₂; HYPO-PCOs) conditions, and morphology, subtype scores, proliferation and drug responses were compared.

resultsSpatial profiling revealed gradients of basal-like-classical heterogeneity across tumours, with basal-like cells enriched in hypoxic regions. HYPO-PCOs tended to retain basal-like traits, including solid or multi-layered morphology, and increased proliferation, along with a tendency toward reduced sensitivity to chemotherapeutic agents. In contrast, NORM-PCOs more often exhibited mono-layered morphology and showed higher classical subtype scores.

conclusionsHypoxic culture conditions promote the preservation of basal-like subpopulations in PDAC organoids, more accurately reflecting the basal-classical heterogeneity of primary tumours. Hypoxia-induced basal-like features remained stable after oxygen switching, indicating a fixed phenotype that informs organoid modelling and offers insight into PDAC progression.

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