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 148patients 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, P<0.001 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 factorA(VEGFA) or Fms related tyrosine kinase1(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.