ArticleClinical cancer research : an official journal of the American Association for Cancer Research2025
HMGA2 Expression Predicts Subtype, Survival, and Treatment Outcome in Pancreatic Ductal Adenocarcinoma.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed.
- Phase 2 study of azacitidine plus pembrolizumab as second-line treatment in patients with locally advanced or metastatic pancreatic ductal adenocarcinoma.The oncologist · 2026Trial
- AI-Powered Deep Visual Proteomics Reveals Critical Molecular Transitions in Pancreatic Cancer Precursors.Cancer discovery · 2026Article
- Identification of mitochondrial-related subtypes and development of a prognostic model for pancreatic ductal adenocarcinoma.Journal of gastrointestinal oncology · 2026Article
- Multimodal profiling of pancreatic cancer reveals a TIMP-1-dominated secretory profile determining pro-tumor immunoinstruction in human cancers.Cell reports. Medicine · 2026Article
- Pancreatic cancer: molecular pathogenesis and emerging therapeutic strategies.Signal transduction and targeted therapy · 2026Review
- HMGA2 links morphological evolution and microenvironment dynamics to systemic therapy response in clear cell renal cell carcinoma.Journal for immunotherapy of cancer · 2025Article
- MicroRNA let-7a mitigates the progression of oral submucous fibrosis by targeting high-mobility group AT-hook 2.Journal of dental sciences · 2025Article
- An allele-agnostic mutant-KRAS inhibitor suppresses tumor maintenance signals and reprograms tumor immunity in pancreatic cancer.Science translational medicine · 2025Article
- GATA6 immunohistochemistry and prognosis after surgical resection of pancreatic adenocarcinoma: results from the ESPAC-4 trial.ESMO gastrointestinal oncology · 2025Article
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22 authors.
Funding
Abstract
purposeThe purpose of this study was to establish HMGA2 as a marker of basal-like disease in pancreatic ductal adenocarcinoma (PDAC) and explore its use as a biomarker for prognosis and treatment resistance. EXPERIMENTAL
designWe identified high-mobility group A2 (HMGA2) protein expression in basal PDAC cells in a single-cell RNA sequencing (RNA-seq) atlas of 172 patient samples. We then analyzed HMGA2 expression, along with expression of the classic marker GATA-binding factor 6 (GATA6), in a cohort of 580 PDAC samples with multiplex IHC. We further supplemented these data with an additional 30 diverse patient samples and multiple independent single-cell RNA-seq databases.
resultsWe found that expression of HMGA2, but not previously described basal markers cytokeratins 5 or 17, predicted overall survival in our cohort. Combining HMGA2 and GATA6 statuses allowed for the identification of two key study groups: an HMGA2+/GATA6- cohort with worse survival, low tumor-infiltrating CD8+ T cells, increased FAP+ fibroblasts, and poorer response to gemcitabine-based chemotherapies (n = 94, median survival = 11.2 months after surgery) and an HMGA2-/GATA6+ cohort with improved survival, increased CD8+ T-cell infiltrate, decreased FAP+ fibroblasts, and improved survival with gemcitabine-based chemotherapy (n = 198, median survival = 21.7 months after surgery). HMGA2 was also prognostic for overall survival in RNA-seq from an independent cohort.
conclusionsIHC stratification of primary tumors by HMGA2 and GATA6 statuses in pancreatic cancer is associated with differential outcomes, survival following chemotherapy, and tumor microenvironments. As a nuclear marker for basal disease, HMGA2 complements GATA6 to identify disease subtypes in PDAC.
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