Protein interaction network analysis of these shared genes revealed that lactoferrin, lipocalin-2 and matrix metalloproteinase-9 are potential key genes in the shared pathophysiology of both diseases.<h4>Conclusions</h4>Our study demonstrates a causal effect of gastric cancer on depression, whereas depression does not exert a causal effect on gastric cancer. Here, LCN2 is linked to major depressive disorder.