Depression, inflammation, and epidermal growth factor receptor (EGFR) status in metastatic non-small cell lung cancer: A pilot study

Patients with stage IV non-small cell lung cancer (NSCLC) have high risk for depressive symptoms and major depressive disorder (MDD); however, those with epidermal growth factor receptor (EGFR) mutations may have decreased risk. The biological underpinning of this relationship is unknown. We examined differences in depression severity and MDD in patients with newly diagnosed stage IV NSCLC based on EGFR mutation status, and examined proinflammatory cytokines and growth factors known to play a role in cancer progression and depression. Fifty-five patients with newly diagnosed stage IV NSCLC completed self-report and clinician-administered depression assessments prior to receiving results of tumor genotyping. We measured serum levels of circulating biological markers of inflammation: IL-1β, IL-6, TGF-α, and TNF-α. We examined differences in depression severity, MDD, and inflammatory biomarkers in patients with and without EGFR mutations. Patients with EGFR mutations (n = 10) had lower depression severity (t[43] = 2.38, p = 0.03) than those without EGFR mutations (n = 38) and fewer patients with EGFR mutations had concurrent MDD (2.08%) relative to those without mutations (27.08%). Patients with MDD had higher levels of TNF-α than those without MDD (t[40] = 2.95, p = 0.005). Those with EGFR mutations exhibited higher levels of TNF-α relative to those without EGFR mutations (t[35] = 2.17, p = 0.04). Patients with stage IV NSCLC harboring an EGFR mutation exhibited elevated proinflammatory marker TNF-α, yet had lower depression severity than patients without EGFR mutations. More work is warranted to examine the interaction between tumor genotyping and inflammatory cytokines in the context of depression.