Expression and prognostic impact of FZDs in pancreatic adenocarcinoma

BACKGROUND: Despite the high number of researches on pancreatic adenocarcinoma (PAAD) over past decades, little progress had been made due to lack of effective treatment regimens. We aimed to investigate the expression level, mutation, and clinical significance of the Frizzled (FZD) family in PAAD so as to establish a sufficient scientific evidence for clinical decisions and risk management. METHODS: PAAD samples were extracted from The Cancer Genome Atlas (TCGA). Oncomine, Gene expression profiling interactive analysis (GEPIA), human protein atlas (HPA), Kaplan–Meier Plotter, cBioPortal, LinkedOmics, DAVID database, and R software (× 64 3.6.2) were used to comprehensively analyze the roles of FZDs. p value below to 0.05 was considered as significant difference. RESULTS: In total, 179 PAAD tissues and 171 paracancerous tissues were included. The expression levels of FZD1, 2, 6, 7, and 8 were higher in PAAD tissues than those in normal pancreatic tissue. The higher the expression levels of FZD2 and FZD7, the higher the clinical stage. The overall survival (OS) time was significantly different between low FZD3, 4, 5, 6, and 9 expression group and high expression group. Multivariable analysis showed that FZD3 and FZD6 were independent prognostic factors. The recurrence free survival (RFS) time was significantly different between low FZD4 and FZD8 expression group and high expression group. The RFS difference between low FZD6 expression group and high expression group had not reached statistical significance (p = 0.067), which might be due to the small sample size. However, multivariable analysis showed that FZD6 was the only independent factor for RFS. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed that FZDs played a critical role in the Wnt signaling pathway, which was further confirmation that FZDs were transmembrane receptors of Wnt signaling pathway. CONCLUSIONS: Our results strongly indicated a crucial role of the FZD family in PAAD. FZD3 and FZD6 could be potential prognostic and predictive markers, and FZD6 might also function as a potential therapeutic target in PAAD by blocking Wnt/β-catenin pathway.