Our comprehensive analysis reveals that immune dysregulation mediated by three mechanism-related genes (BHLHE41, EpCAM, and GSTM2) through MAPK pathway activation, coupled with their dual promotion of neuroinflammation and EMT, forms the comorbid mechanism network between depression and BC, establishing a fundamental biological link underlying their co-occurrence. The gene discussed is EPCAM; the disease is depressive symptom measurement.