Depression in association with neutrophil-to-lymphocyte, platelet-to-lymphocyte, and advanced lung cancer inflammation index biomarkers predicting lung cancer survival

Abstract

Lung cancer is a product of inflammation and a dysfunctional immune system, and depression has similar dysregulation. Depression disproportionately affects lung cancer patients, having the highest rates of all cancers. Systemic inflammation and depression are both predictive of non-small cell lung cancer (NSCLC) survival, but the existence and extent of any co-occurrence is unknown. Studied is the association between systemic inflammation ratio (SIR) biomarker levels and patients’ depressive symptoms, with the hypothesis that depression severity would be significantly associated with prognostically poor inflammation. Newly diagnosed stage-IV non-small cell lung cancer (NSCLC; N = 186) patients were enrolled (ClinicalTrials.gov Identifier: NCT03199651) and blood draws and depression self-reports (Patient Health Questionnaire-9) were obtained. For SIRs, cell counts of neutrophils (N), lymphocytes (L), and platelets (P) were abstracted for ratio (R) calculations for NLR, PLR, and the Advanced Lung cancer Inflammation Index (ALI). Patients were followed and biomarkers were tested as predictors of 2-year overall survival (OS) to confirm their relevance. Next, multivariate linear regressions tested associations of depression with NLR, PLR, and ALI. Overall 2-year mortality was 61% (113/186). Cox model analyses confirmed higher NLR [hazard ratio (HR) = 1.91; p = 0.001] and PLR (HR = 2.08; p<0.001), along with lower ALI (HR = 0.53; p = 0.005), to be predictive of worse OS. Adjusting for covariates, depression was reliably associated with biomarker levels (p ≤ 0.02). Patients with moderate/severe depressive symptoms were 2 to 3 times more likely to have prognostically poor biomarker levels. Novel data show patients’ depressive symptoms were reliably associated with lung-relevant systemic inflammation biomarkers, all assessed at diagnosis/pretreatment. The same SIRs were found prognostic for patients’ 2-year OS. Intensive study of depression, combined with measures of cell biology and inflammation is needed to extend these findings to discover mechanisms of depression toxicity for NSCLC patients’ treatment responses and survival.