Depression induces poor prognosis associates with the down-regulation brain derived neurotrophic factor of serum in advanced small cell lung cancer

Oncotarget. 2016 Dec 27;7(52):85975-85986. doi: 10.18632/oncotarget.13291.

Abstract

Patients with lung cancer often experience a state of depression, and these conditions may severely affect their quality of life (QoL) and prescription compliance. The current study was conducted to delineate the complex links between depression and the prognosis of patients with small cell lung cancer (SCLC) and the underlying mechanism was also explored.186 patients who received platinum-based chemotherapy for newly diagnosed stage III or stage IV SCLC were enrolled. The Self-Rating Depression Scale (SDS) questionnaire was completed the day before the start of chemotherapy to assess the depression status of the patients. Patients with stage IV SCLC or lower BMI have higher depression scores. In terms of the adverse effects of chemotherapy, depression severely decreases patient tolerance to chemotherapy and their QoL score (R2 = 0.2385) and is also associated with severe vomiting (P < 0.001), leukopenia (R2 = 0.2332), and prolonged hospital stay (R2 = 0.1961). More importantly, severe depression reduces the PFS (R2 = 0.1943) and OS (P < 0.01) of the patients. We found that patients with severe depression displayed a downregulated level of serum BDNF and that the level of serum BDNF was highly correlated with the OS of the patients (R2 = 0.2292). Using the MTT cell viability assay in vitro, we observed that cotreatment with BDNF clearly enhanced the chemosensitivity of NCI-H69 tumor cells to Cisplatin and induced the downregulation of ABCG2.Based on this evidence, it appears that a relationship does exist between depression and prognosis in SCLC and that the mechanism by which depression affects prognosis is achieved via the downregulation of BDNF expression.

Keywords: ABCG2; brain derived neurotrophic factor; chemotherapy; depression; small cell lung cancer.

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily G, Member 2 / physiology
  • Aged
  • Brain-Derived Neurotrophic Factor / blood*
  • Cell Line, Tumor
  • Depression / blood*
  • Down-Regulation
  • Drug Resistance, Neoplasm
  • Female
  • Humans
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / mortality*
  • Lung Neoplasms / psychology
  • Male
  • Middle Aged
  • Prognosis
  • Quality of Life
  • Small Cell Lung Carcinoma / drug therapy
  • Small Cell Lung Carcinoma / mortality*
  • Small Cell Lung Carcinoma / psychology

Substances

  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • Brain-Derived Neurotrophic Factor
  • BDNF protein, human