Correlation analysis of depressive symptoms and immune function indicators in patients with malignant melanoma

Abstract

BACKGROUND

Malignant melanoma carries the highest mortality among skin cancers and is frequently complicate by depression, which may worsen prognosis. Emerging psychoneuroimmunology evidence links depressive states to suppressed cellular immunity and chronic inflammation, but large-scale studies specifically in melanoma are lacking.

AIM

To investigate the correlation between depressive symptoms and immune function indicators in patients with malignant melanoma, identify independent risk factors affecting depressive symptoms, and provide scientific evidence for clinical psychological intervention and immunomodulatory therapy.

METHODS

Clinical data of 202 patients with malignant melanoma from January 2019 to March 2025 were retrospectively analyzed. Patient Health Questionnaire-9, Pittsburgh Sleep Quality Index, Fatigue Severity Scale, and Perceived Stress Scale-10 were used to assess depressive symptoms. Cellular immune indicators [CD3+, CD4+, CD8+, natural killer (NK) cell counts and percentages], humoral immune indicators (immunoglobulins, complement C3, C4), inflammatory factors [interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), IL-10, interferon gamma, C-reactive protein, erythrocyte sedimentation rate], and routine blood biochemical indicators were detected. Pearson and Spearman correlation analyses were used to explore the relationship between depressive symptoms and immune indicators, multiple linear regression analysis was used to analyze independent influencing factors, and receiver operating characteristic curves were used to evaluate predictive efficacy.

RESULTS

Among 202 patients, 113 (55.9%) developed depressive symptoms. Patients in the depression group had significantly lower CD3+ cell count, CD4+ cell count, NK cell count, and CD4+/CD8+ ratio (all P < 0.05); complement C3 and C4 levels were decreased (all P < 0.05); IL-6, TNF-α, C-reactive protein, erythrocyte sedimentation rate, and neutrophil-to-lymphocyte ratio (NLR) levels were elevated, while IL-10 and interferon gamma were decreased (all P < 0.05). Patient Health Questionnaire-9 scores were positively correlated with IL-6 (r = 0.456), TNF-α (r = 0.398), and NLR (r = 0.418), and negatively correlated with CD4+ cell count (r = -0.367) and NK cell count (r = -0.298) (all P < 0.001). Multiple regression analysis showed that IL-6 (β = 0.365), tumor-node-metastasis stage (β = 0.178), and NLR (β = 0.198) were positive predictors of depressive symptoms, while CD4+ cell count (β = -0.234) and albumin (β = -0.124) were negative predictors (all P < 0.05), with model R² = 0.524. The area under the curve of IL-6 for predicting depressive symptoms was 0.782, and the combined multi-indicator model area under the curve was 0.834.

CONCLUSION

Depressive symptoms in patients with malignant melanoma are closely associated with cellular immune function suppression and chronic inflammatory responses, and immune indicators such as IL-6 can serve as effective predictors for assessing depression risk.

Keywords: Malignant melanoma; Depressive symptoms; Immune function; Cellular immunity; Inflammatory factors

Core Tip: This retrospective study revealed that over half of malignant melanoma patients experienced depressive symptoms, which were closely associated with suppressed cellular immunity and elevated inflammatory markers such as interleukin-6 (IL-6) and neutrophil-to-lymphocyte ratio. CD4+ T cell count and serum albumin were found to be protective factors, while IL-6 and advanced tumor-node-metastasis stage were risk predictors. A multi-indicator model combining IL-6, CD4+, and neutrophil-to-lymphocyte ratio achieved good predictive performance (area under the curve = 0.834). These findings highlight the need for integrated psychosocial and immunological assessment in melanoma patients to improve mental health and potentially affect prognosis.