ArticleCancer discovery2023
Spatial Transcriptomics of Intraductal Papillary Mucinous Neoplasms of the Pancreas Identifies NKX6-2 as a Driver of Gastric Differentiation and Indolent Biological Potential.
Article in Cancer discovery, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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44 citing papers in PubMed, 57 citations in OpenAlex.
- Asynchronous Evolution of Epithelium and Stroma Differentiates Precursor Lesions from Pancreatic Cancer.Cancer discovery · 2026Article
- Spatially resolved tissue architecture and computational pathology in pancreatic cancer.Experimental & molecular medicine · 2026Review
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- Molecular pathology of intraductal papillary mucinous neoplasms of the pancreas: current understanding and perspectives on malignant progression.Journal of gastroenterology · 2026Review
- Spatial transcriptomics in cancer research: insights into tumorigenesis, diagnosis and therapeutics.Cell death discovery · 2026Review
- A systematic scoping review of the molecular pathogenesis of digestive system cancers (2013-2025).Discover oncology · 2026Article
- Pan-cancer analysis of spatial transcriptomics reveals heterogeneous tumor spatial microenvironment.Cell reports. Medicine · 2026Article
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- Benchmarking tools for deciphering cellular crosstalk in spatially-resolved transcriptomics.Genome biology · 2026Article
- UniST: A Unified Computational Framework for 3D Spatial Transcriptomics Reconstruction.bioRxiv : the preprint server for biology · 2026Article
- Atlas-Guided Nanocarrier Strategies Targeting Spatial NTRK2/MAPK Signaling in EGFR-TKI-Resistant Niches of Esophageal Squamous Cell Carcinoma.Pharmaceutics · 2026Review
- Spatial Analysis of Intraductal Papillary Mucinous Neoplasms Defines a Paradoxical Keratin 17-Positive, Low-Grade Epithelial Population Harboring Malignant Features.Cellular and molecular gastroenterology and hepatology · 2026Article
- Multi-omics and experimental validation identify USP54 as a prognostic deubiquitinase promoting pancreatic ductal adenocarcinoma progression within the immune microenvironment.Frontiers in immunology · 2026Article
- Mutant GNAS drives a pyloric metaplasia with tumor suppressive glycans in intraductal papillary mucinous neoplasia.Cell reports · 2025Article
- Review
- Integrative analysis of genomic and transcriptomic data informs precancer progression in the pancreas.bioRxiv : the preprint server for biology · 2025Article
- Spatial profiling of human pancreatic ductal adenocarcinoma reveals molecular alterations associated with venous invasion.Science translational medicine · 2025Article
- Article
- Spatial and temporal dynamics in progressive gallbladder cancer.Nature genetics · 2025Article
- Cyst fluid proteins stratify malignant risk of intraductal papillary mucinous neoplasm of the pancreas.Cancer letters · 2025Article
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15 authors at 2 institutions in 1 country.
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Abstract
Intraductal papillary mucinous neoplasms (IPMN) of the pancreas are bona fide precursor lesions of pancreatic ductal adenocarcinoma (PDAC). The most common subtype of IPMNs harbors a gastric foveolar-type epithelium, and these low-grade mucinous neoplasms are harbingers of IPMNs with high-grade dysplasia and cancer. The molecular underpinning of gastric differentiation in IPMNs is unknown, although identifying drivers of this indolent phenotype might enable opportunities for intercepting progression to high-grade IPMN and cancer. We conducted spatial transcriptomics on a cohort of IPMNs, followed by orthogonal and cross-species validation studies, which established the transcription factor NKX6-2 as a key determinant of gastric cell identity in low-grade IPMNs. Loss of NKX6-2 expression is a consistent feature of IPMN progression, while reexpression of Nkx6-2 in murine IPMN lines recapitulates the aforementioned gastric transcriptional program and glandular morphology. Our study identifies NKX6-2 as a previously unknown transcription factor driving indolent gastric differentiation in IPMN pathogenesis. SIGNIFICANCE: Identification of the molecular features driving IPMN development and differentiation is critical to prevent cancer progression and enhance risk stratification. We used spatial profiling to characterize the epithelium and microenvironment of IPMN, which revealed a previously unknown link between NKX6-2 and gastric differentiation, the latter associated with indolent biological potential. See related commentary by Ben-Shmuel and Scherz-Shouval, p. 1768. This article is highlighted in the In This Issue feature, p. 1749.
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