AREG and cancer: Expression of SPHK1 was significantly correlated with that of genes such as IL6, ITGA2, IL8, EREG, MMP1, ITGA5, MMP3 and AREG. Most of these genes are the downstream genes of the EGFR pathway, and most of them such as EREG [33,34], MMP1 [35] and AREG [33,34] have been reported to be associated with the invasion of cancer cells.