Wang Dazhi1,2, Jiao Zheng1, Ren Chunling3. 1. Center for Precision Cancer Medicine, Clinical Oncology Pharmacist Training Bases (National Health Commission), Department of Pharmacy, Qingdao Municipal Hospital, Qingdao University, Qingdao, 266071, China. 2. Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, 44, West Culture Road, 250012, Jinan, Shandong, China. 3. Qingdao Women & Children's Hospital, School of Medicine, Qingdao University, Qingdao, 266071, China.
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.
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.