Abstract

BACKGROUND: Fibroblast growth factor receptors (FGFRs) play vital roles in the development and progression of human cancers. This study aimed to comprehensively understand the prognostic performances of FGFR1-4 expression in breast cancer (BC) by mining databases.

MATERIAL AND METHODS: The levels of FGFR1-4 expression in BC were analyzed by online databases, GEPIA (Gene Expression Profiling Interactive Analysis) and UALCAN. Survival analysis of FGFR1-4 was carried out by Kaplan-Meier plotter. GSE74146 was downloaded from Gene Expression Omnibus (GEO) and analyzed by GEO2R to screen the differentially expressed genes (DEGs) between FGFR2-silenced BC cells and control. Over-presentation for DEGs were done by Enrichr tool. Networks of DEGs were obtained by using Search Tool for the Retrieval of Interacting Genes (STRING) and Cytoscape software. Hub genes were identified by cytoHubba Cytoscape plugin.

RESULTS: The online databases showed that FGFR1 was significantly downregulated whereas FGFR3 was upregulated in BC. Kaplan-Meier plotter demonstrated the upregulation of both FGFR1 and FGFR3 indicated favorable relapse free survival (RFS) whereas FGFR4 overexpression predicted unfavorable overall survival (OS) in BC patients. Importantly, our results showed FGFR2 overexpression robustly predicted favorable OS and RFS in BC. Further bioinformatics analysis of GSE74146 suggested FGFR2 mainly participated in regulating degradation and organization of the extracellular matrix and signaling of retinoic acid. Moreover, CXCL8, CD44, MMP9, and BMP7 were identified as crucial FGFR2-related hub genes.

CONCLUSIONS: Our study comprehensively analyzed the prognostic values of FGFR1-4 expression in BC and proposed FGFR2 might serve as a promising biomarker. However, the underlying mechanisms remain to be elucidated.

Keywords: Breast Neoplasms, Computational Biology, Receptor, Fibroblast Growth Factor, Type 2, Databases, Genetic, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Gene Regulatory Networks, Prognosis, Protein Interaction Maps, Receptors, Fibroblast Growth Factor, Signal Transduction