High DAPK1 Expression Promotes Tumor Metastasis of Gastric Cancer

SIMPLE SUMMARY: Gastric cancer is a common upper gastrointestinal tumor. Death-associated protein kinase (DAPK1) was found to participate in the development of various malignant tumors. However, there are few reports on DAPK1 in gastric cancer. In this study, we found that the expression of DAPK1 was up-regulated in gastric cancer tissues. Survival analysis showed that low expression of DAPK1 was a favorable prognostic factor of overall survival and disease-free survival for gastric cancer patients. The functional experiments demonstrated that DAPK1 can promote the migration and invasion of gastric cancer cells. Meanwhile, a risk score module for four DAPK1-related genes was constructed and validated. In conclusion, these results indicated that DAPK1 can promote gastric cancer cell migration and invasion and established a signature of four DAPK1-related genes for gastric cancer that could independently predict the survival of gastric cancer patients. ABSTRACT: Gastric cancer (GC) is a common upper gastrointestinal tumor. Death-associated protein kinase (DAPK1) was found to participate in the development of various malignant tumors. However, there are few reports on DAPK1 in gastric cancer. In this study, the TCGA and GEO datasets were used to explore the expression and role of DAPK1 in gastric cancer. The functions of DAPK1 in gastric cancer were determined by proliferation, migration and invasion assays. In addition, genes co-expressed with DAPK1 in gastric cancer were estimated through the WGCNA and correlation analysis. A DAPK1-related gene prognostic model was constructed using the Cox regression and lasso analyses. The expression of DAPK1 was significantly up-regulated in gastric cancer tissues. Kaplan–Meier analysis showed that low expression of DAPK1 was a favorable prognostic factor of overall survival and disease-free survival for gastric cancer patients. Functional experiments demonstrated that DAPK1 can promote the migration and invasion of gastric cancer cells. WGCNA, correlation analysis, Cox regression, and lasso analyses were applied to construct the DAPK1-related prognostic model. The prognostic value of this prognostic model of DAPK1-related genes was further successfully validated in an independent database. Our results indicated that DAPK1 can promote gastric cancer cell migration and invasion and established four DAPK1-related signature genes for gastric cancer that could independently predict the survival of GC patients.