High ELK3 expression is associated with the VEGF-C/VEGFR-3 axis and gastric tumorigenesis and enhances infiltration of M2 macrophages

Abstract

Aim: To assess the expression and effect of ELK3 in gastric cancer, along with its associations with the VEGF-C/VEGFR-3 axis, IC50 of the VEGFR-3 inhibitor axitinib and immune infiltration of M2-polarized macrophages in gastric cancer, and to analyze the possible epigenetic regulation mechanism. Materials & methods: Expression profiles and methylation data from 1645 samples were obtained and examined from multi-institutional public datasets. The associations were assessed by multiple analysis methods. Results: Elevated ELK3 is associated with the VEGF-C/VEGFR-3 axis and tumorigenesis, reduces the effect of axitinib in vitro, enhances immune infiltration of M2 macrophages and affects clinical outcomes. Hypomethylation contributes to the upregulation of ELK3 in gastric cancer. Conclusions: ELK3 is a potential therapeutic target which reduces the effect of axitinib and enhances infiltration of M2-polarized macrophages.