FGFR1 signaling potentiates tumor growth and predicts poor prognosis in esophageal squamous cell carcinoma patients.

Abstract

Fibroblast growth factor receptor-1 (FGFR1) over-expression was broadly found in squamous cancer, where it induced cellular proliferation, differentiation, and metastasis by activating various signaling pathway. However, the role of FGFR1 gene expression in predicting prognosis of Esophageal Squamous Cell Carcinoma (ESCC) and its regulatory function in the progression of ESCC are not well understood. Therefore, we performed an analysis of FGFR1 mRNA expression by quantitative RT-PCR in tumor tissue of 145 patients with ESCC. The relationships between FGFR1 gene expression and clinicopathological parameters, also the prognosis were further examined. Results suggested that higher FGFR1 gene expression predicted worse overall survival (HR = 1.502, 95%[CI] = 1.005-2.246, P = 0.045). Disease-free survival tends to be shorter in patients with higher FGFR1 expression but without statistical significance (HR = 1.398, 95%[CI] = 0.942-2.074, P = 0.096). FGFR1 was up regulated in multiple ESCC cell lines. Subsequent in vitro experiments demonstrated that anti-FGFR1 treatment by PD173074 inhibited TE-1 and EC9706 cell viability along with the attenuation of MEK-ERK signaling pathway. In vivo, PD173074 administration also had shown potent ESCC growth arresting effect. Overall, our study suggested that FGFR1 gene expression could be an independent prognosis predictive factor in patients with ESCC. Anti-FGFR1 inhibited ESCC growth and could be a potential strategy in ESCC targeted therapy.

• Authors: Baoqing Chen, Shurui Liu, Lu Gan, Jingwen Wang, Binbin Hu, He Xu, Ruizhan Tong, Hui Yang, Ivan Cristina, Jianxin Xue, Xun Hu, You Lu
• Journal: Cancer biology & therapy (Cancer Biol Ther) Vol. 19 Issue 1 Pg. 76-86 (01 02 2018) ISSN: 1555-8576 [Electronic] United States
• PMID: 29257923 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• PD 173074
• Pyrimidines
• RNA, Messenger
• FGFR1 protein, human
• Receptor, Fibroblast Growth Factor, Type 1

Topics

• Aged
• Animals
• Antineoplastic Agents (pharmacology, therapeutic use)
• Apoptosis (drug effects)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Cell Survival (drug effects)
• Disease Progression
• Disease-Free Survival
• Esophageal Neoplasms (pathology)
• Esophageal Squamous Cell Carcinoma (pathology)
• Female
• Humans
• Kaplan-Meier Estimate
• MAP Kinase Signaling System (drug effects)
• Male
• Mice, Nude
• Prognosis
• Pyrimidines (pharmacology, therapeutic use)
• RNA, Messenger (metabolism)
• Receptor, Fibroblast Growth Factor, Type 1 (antagonists & inhibitors, genetics, metabolism)
• Treatment Outcome
• Xenograft Model Antitumor Assays