This study demonstrates that TRAIL may be a useful agent inducing cell apoptosis in cisplatin-resistant human GC cells and that JWA functions as an upstream regulator that promotes the ubiquitination of DR4 at K273 via the upregulation of the ubiquitin ligase MARCH8, thus indicating that JWA is a potential predictive marker for TRAIL sensitivity that may improve personalized therapeutics for human GC. This evidence concerns the gene TNFRSF10A and gastric cancer.