ArticleAnnals of surgical oncology2025
Overexpression of Nuclear Factor of Activated T-cells (NFAT) Transcription Factors Drives Chemoresistance and Poor Outcomes in Pancreatic Cancer.
Article in Annals of surgical oncology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
1 citing paper in PubMed.
- Dihydroartemisinin alleviates pulmonary fibrosis by modulating the calcium signaling pathway in fibroblasts.Journal of translational medicine · 2025Article
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Authors and funding
19 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundPancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal malignancies with high recurrence and poor survival (5-year survival rate: approximately 10%) despite curative resection. Identifying molecular drivers of PDAC recurrence remains a significant challenge. PDAC is characterized by dense stromal hyperplasia that may influence tumor cell-specific gene expression. We aimed to identify genes associated with early recurrence using patient-derived xenograft (PDX) models, focusing on the calcineurin-nuclear factor of activated T-cells (NFAT) signaling pathway. MATERIALS AND
methodsGene expression profiles were analyzed in PDX models derived from PDAC tumors. Differential gene expression (DEG) analysis was conducted to identify pathways linked to early recurrence. Immunohistochemical (IHC) analysis of 165 resected PDAC specimens was performed to evaluate NFAT protein expression. Multivariate Cox regression identified independent prognostic factors for recurrence and survival. Chemoresistance was examined by silencing NFAT1 and NFAT5 in PDAC cell lines and measuring changes in the half-maximal inhibitory concentration (IC
resultsDEG analysis revealed enrichment of the calcineurin-NFAT signaling cascade. Higher expression of NFAT1 and NFAT5 were significantly associated with early recurrence. IHC revealed NFAT1 expression in 53 (32.1%) samples, NFAT5 in 104 (63.0%), and coexpression in 43 (26.1%). Multivariate analysis identified lymphatic invasion, incomplete resection, and NFAT1/NFAT5 coexpression as independent predictors of poor prognosis. Dual knockdown of NFAT1 and NFAT5 significantly reduced the IC
conclusionsCoexpression of NFAT1 and NFAT5 is associated with early recurrence, poor survival, and chemoresistance in PDAC. Targeting the NFAT signaling pathway may improve treatment outcomes in PDAC.
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