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Prog Neuropsychopharmacol Biol Psychiatry. 2013 Dec 2;47:69-76. doi: 10.1016/j.pnpbp.2013.08.004. Epub 2013 Aug 19.

Sputum interleukin-6, tumor necrosis factor-α and Salivary cortisol as new biomarkers of depression in lung cancer patients.

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Lab of Integrative Medicine for Lung, Inflammation and Cancers, Huashan Hospital, Fudan University, Shanghai, China.


Depression is common among lung cancer patients. Increasing evidence has suggested that hypothalamic-pituitary-adrenal (HPA) axis and pro-inflammatory cytokines may play a key role in the pathophysiology of depression as well as cancer. This pilot study investigated the efficacy of sputum interleukin (IL)-6, tumor necrosis factor (TNF)-α and salivary cortisol as new markers to support the diagnosis of depression in lung cancer patients. The diurnal rhythms of sputum IL-6, sputum TNF-α and salivary cortisol were measured in lung cancer patients with and without depression as well as depressed controls and healthy controls. The area under the diurnal variation curves (AUC) over the 24h time course and relative diurnal variation (VAR) were calculated. Receiver operating characteristic (ROC) analysis was performed. Patients with co-morbid depression and lung cancer showed highest level of sputum IL-6 AUC, sputum TNF-α AUC and lowest level of cortisol VAR (P<0.001). As a biomarker for depression, salivary cortisol VAR demonstrated an optimal cutoff point at 77.8% (AUC=0.94; 95% CI, 0.85-0.98), which is associated with a sensitivity of 82.1% and a specificity of 96.0%. Sputum IL-6 AUC demonstrated a sensitivity of 74.4% and a specificity of 92.0% (AUC=0.81; 95% CI, 0.69-0.90). These findings suggested that higher 24h overall levels of sputum IL-6, TNF-α and flattened diurnal salivary cortisol slopes were associated with depression in lung cancer patients. Sputum IL-6 AUC and salivary cortisol VAR performed best as biomarkers in the diagnosis of depression in lung cancer patients.


ANOVA; AUC; Biomarkers; CI; Cortisol; Cytokines; Depression; Diurnal rhythm; FEV1; FVC; HADS; HAM-D; HPA; Hamilton Depression Rating Scale; Hospital Anxiety and Depression Scale; IL-6; KPS; Karnofsky Performance Status; Lung cancer; PEF; QOL; Quality of Life; RIA; ROC; SD; TNF-α; VAR; area under the diurnal variation curves; confidence interval; forced expiratory volume in 1s; forced vital capacity; hypothalamic–pituitary–adrenal; interleukin-6; one way analysis of variance; peak expiratory flow; radioimmunoassay; receiver operating characteristic; relative diurnal variation; standard deviation; tumor necrosis factor-α

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