Journal Article

High FGFR4 protein expression, but not FGFR1 or FGFR2, predicts poor prognosis in pancreatic ductal adenocarcinoma

Antosik, Paulina, Braun, Marcin, Durślewicz, Justyna, Zielińska, Aleksandra, Nowicka, Zuzanna, Grzanka, Dariusz, Sołek, Julia

2025

Overview

Background The number of prognostic and predictive factors for pancreatic ductal adenocarcinoma (PDAC) is limited. Fibroblast growth factor receptors (FGFRs) are emerging as potential therapeutic targets, especially in cases with FGFR2 gene fusions. However, the prognostic relevance of FGFR1, FGFR2, and FGFR4 protein expression in PDAC remains unclear. Methods Immunohistochemical analysis of FGFR1, FGFR2, and FGFR4 was performed on 99 PDAC and 60 adjacent normal pancreatic tissue samples. Protein expression was quantified using the H-score method and correlated with clinicopathological variables and survival. Publicly available datasets from the GEO repository and the cancer genome atlas (TCGA) were used for pathway enrichment analysis and validation of findings at the mRNA level. Results FGFR2 and FGFR4 showed differential expression between tumor and normal tissues, while FGFR1 did not. High FGFR4 protein expression was significantly associated with shorter disease-free survival (DFS) in both univariable and multivariable analyses. FGFR2 high expression cases showed a trend towards poor DFS, while FGFR1 had no prognostic impact. In silico analysis confirmed that high FGFR4 mRNA levels are associated with worse DFS. Co-expression and enrichment analysis linked FGFR4 overexpression with developmental, metabolic, and stemness-related processes. Conclusion FGFR4 showed the strongest prognostic association among the FGFR family members studied, with high protein expression correlating with shorter disease-free survival in PDAC patients. These findings underscore the potential of FGFR4 as a biomarker for recurrence risk, while also highlighting the complexity of FGFR-related signaling and its context-dependent clinical relevance.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Adenocarcinoma / Adult / Aged / Biomarkers, Tumor - genetics / Biomarkers, Tumor - metabolism / Biomedical and Life Sciences / Biomedicine / Cancer Research / Carcinoma, Pancreatic Ductal - genetics / Carcinoma, Pancreatic Ductal - metabolism / Carcinoma, Pancreatic Ductal - mortality / Carcinoma, Pancreatic Ductal - pathology / Cloning / Development and progression / Female / FGFR / Fibroblast growth factor receptor / Fibroblast growth factor receptor 1 / Fibroblast growth factor receptor 2 / Fibroblast growth factor receptor 4 / Fibroblast growth factor receptors / Gene expression / Gene Expression Regulation, Neoplastic / Growth factor receptors / Health aspects / Health Promotion and Disease Prevention / Humans / Immunohistochemistry / Kopernik, Mikolaj (Nicolaus Copernicus) (1473-1543) / Male / Medical prognosis / Medicine/Public Health / Middle Aged / mRNA / Normal distribution / Oncology / Pancreas / Pancreatic cancer / Pancreatic ductal adenocarcinoma / Pancreatic Neoplasms - genetics / Pancreatic Neoplasms - metabolism / Pancreatic Neoplasms - mortality / Pancreatic Neoplasms - pathology / PDAC / Physiological aspects / Prognosis / Protein expression / Proteins / Receptor, Fibroblast Growth Factor, Type 1 - genetics / Receptor, Fibroblast Growth Factor, Type 1 - metabolism / Receptor, Fibroblast Growth Factor, Type 2 - genetics / Receptor, Fibroblast Growth Factor, Type 2 - metabolism / Receptor, Fibroblast Growth Factor, Type 4 - genetics / Receptor, Fibroblast Growth Factor, Type 4 - metabolism / Surgery / Surgical Oncology / Survival / Therapeutic targets / Tumors