Colony-stimulating factor-1 and colony-stimulating factor-1 receptor co-expression is associated with disease progression in gastric cancer

Abstract

Colony-stimulating-factor-1 (CSF-1) is a hematopoietic growth factor that exerts its effects through the c-fms/CSF-1 receptor (CSF-1R). The CSF-1/CSF-1R axis is thought to be involved in the development of several types of cancer. This study aimed to clarify the clinical and biological significance of the CSF-1/CSF-1R axis in gastric cancer (GC). For this purpose, we evaluated CSF-1 and CSF-1R expression in GC tissues from 148 patients by RT-qPCR and immunohistochemistry. The biological roles of the CSF-1/CSF-1R axis were investigated by measuring the cell proliferation and migration, and anoikis resistance in a human GC cell line following treatment with recombinant human CSF-1 and/or CSF-1R inhibitor. The results revealed that an elevated expression of CSF-1 or CSF-1R significantly correlated with disease progression and with a poor overall survival (OS, P=0.037 and 0.016, respectively) and disease-free survival (DFS, P0.001 and 0.001, respectively) of patients with GC. Furthermore, a high co-expression of CSF-1 and CSF-1R was an independent prognostic factor for OS (HR, 1.38; 95% CI, 1.02-1.88; P=0.038) and DFS (HR, 1.79; 95% CI, 1.21-2.67; P=0.004), and an independent risk factor for lymph node and peritoneal metastasis. Immunohistochemical analysis revealed an intense CSF-1/CSF-1R expression in the cytoplasm of cancer cells in primary GC tissues. CSF-1 or CSF-1R expression positively correlated with vascular endothelial growth factor A (VEGFA) or Fms related tyrosine kinase 1 (FLT1) expression in GC tissues. Treatment with recombinant human CSF-1 promoted proliferation, migration and anoikis resistance in a GC cell line. These effects were generally blocked by CSF-1R inhibition. On the whole, the findings of this study indicate that the CSF-1/CSF-1R axis may be a clinically useful prognostic and predictive biomarker for lymph node and peritoneal metastasis and a potential therapeutic target in GC.