Fibroblast growth factor 8 overexpression is predictive of poor prognosis in pancreatic ductal adenocarcinoma

Abstract

Summary Background Despite distinctive advances in the field of pancreatic cancer therapy over the past few years, patient survival remains poor. Fibroblast growth factors 8 (FGF8) and 18 (FGF18) both play a role in modulating the activity of malignant cells and have been identified as promising biomarkers in a number of cancers. However, no data exist on the expression of FGF8 and FGF18 in pancreatic ductal adenocarcinoma (PDAC). Methods Protein expression levels of FGF8 and FGF18 in postoperative specimens of neoadjuvantly treated and primarily resected patients were investigated using immunohistochemistry. Immunostaining scores were calculated as the products of the staining intensity and the staining rate. Scores exceeding the median score were considered as high expression. Results Specimens from 78 patients with PDAC were available and met the eligibility criteria for analysis of protein expression using immunohistochemistry. 15 (19.2%) patients had received neoadjuvant chemotherapy. High protein levels of FGF8 and FGF18 were detected in 40 (51.8%) and 33 (42.3%) patients, respectively. Kaplan–Meier analysis demonstrated significantly shorter overall survival in patients with high expression of FGF8 (p = 0.04). Multivariable Cox proportional hazard regression models revealed that high expression of FGF8 (Hazard ratio [HR] 0.53, 95% Confidence interval [CI] 0.32–0.89, p = 0.016) was an independent prognostic factor for diminished overall survival in patients with PDAC. By contrast, no statistical significance was found for FGF18 overexpression. In addition, the FGF8 protein level correlated with the factor resection margin (p = 0.042). Conclusion FGF8 is a promising target for new anticancer therapies using FGF inhibitors in pancreatic ductal adenocarcinomas.