Finally, qRT-PCR validated the alternations of depression-related genes in depression-like mouse models, and <i>in vitro</i> experiments confirmed that PSEN1 facilitated cell proliferation in LUAD.<h4>Conclusions</h4>The molecular profile defined by the DRS can serve as an independent overall survival predictor and improve individualized treatment and clinical decision for LUAD patients. Here, PSEN1 is linked to major depressive disorder.