Identification of an immune-metabolic biosignature linking depressive symptoms and breast cancer in a clinical population

Breast cancer (BC) is a leading cause of mortality among women. Comorbidity with mood disorders is a condition either disregarded or underdiagnosed in BC patients, but that might ultimately jeopardize health trajectories. This is supported by evidence indicating that the same biological pathways relevant for mood disorders may also underlie tumorigenesis. In this study, we aimed at deriving a reliable biosignature of mental health vulnerability in BC patients. We conducted a cross-sectional study in a population of women diagnosed with BC who underwent surgery before receiving adjuvant chemotherapy. All subjects were scored for symptoms of depression, anxiety and stress; blood samples were used to measure relevant biomarkers of inflammation, energy homeostasis and brain plasticity, while circadian cortisol rhythm was assessed in the saliva. Based on a rigorous statistical approach, we identified a specific immune- metabolic biosignature of depression relying upon each subject’s BMI, IL-5 and leptin. Following the validation of the model, we defined a cut-off value to identify those subjects who are at elevated risk of poor prognosis based on our biosignature. This signature holds potential for the timely identification of those individuals for whom depressive symptoms are sustained by a deranged immune-metabolic milieu and might therefore be at higher risk of poorer health outcomes. Our results strengthen the importance of accounting for brain-body communication in cancer and suggest that routine screening for mental health in BC patients should be prioritized in order to put in place tailored intervention strategies to improve health outcomes.