RAPGEF5 and neoplasm: Neurotrophic factors, including nerve growth factor (NGF), glial cell line-derived neurotrophic factor (GDNF) and NT3 secreted from nerve were rich in the nerve-tumor microenvironment and acted as prominent promoters in PNI through respectively combining with their receptor, tyrosine kinase A receptor (TRKA), GDNF family receptors (GFR) and NT-3, expressed by tumor cells of pancreatic, breast and bile duct carcinomas [7].