This was first study suggested there were a negative correlation between LFNG, MFNG and RFNG expression and its DNA methylation, suggesting a critical role of epigenetic regulation, one potential mechanism is the activation of NOTCH signaling by LFNG, MFNG and RFNG, resulting in invasive growth and migration of pancreatic cancer cells. This evidence concerns the gene RFNG and familial pancreatic carcinoma.