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

// Yufeng Wu 1 , Ruirui Si 2 , Sen Yang 1 , Suhua Xia 3 , Zelai He 4 , Lili Wang 1 , Zhen He 1 , Qiming Wang 1 , Hong Tang 1 1 Department of Internal Medicine, Affiliated cancer hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, Henan, 450008, P. R. China 2 Department of Health Center, Henan Airport Group Co., Ltd., Henan, 450000, P. R. China 3 Department of Oncology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, 215006, P. R. China 4 Department of Oncology, The 2nd Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, PR China Correspondence to: Qiming Wang, email: qimingwang1006@163.com Hong Tang, email: 852261201@qq.com Keywords: depression, chemotherapy, small cell lung cancer, brain derived neurotrophic factor, ABCG2 Received: August 04, 2016      Accepted: November 07, 2016      Published: November 11, 2016 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 (R 2 = 0.2385) and is also associated with severe vomiting ( P < 0.001), leukopenia (R 2 = 0.2332), and prolonged hospital stay (R 2 = 0.1961). More importantly, severe depression reduces the PFS (R 2 = 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 (R 2 = 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.