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抑郁症会导致晚期小细胞肺癌患者预后不良,这与血清中脑源性神经营养因子的下调有关。

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

作者信息

Wu Yufeng, Si Ruirui, Yang Sen, Xia Suhua, He Zelai, Wang Lili, He Zhen, Wang Qiming, Tang Hong

机构信息

Department of Internal Medicine, Affiliated cancer hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, Henan, 450008, P. R. China.

Department of Health Center, Henan Airport Group Co., Ltd., Henan, 450000, P. R. China.

出版信息

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.

摘要

肺癌患者常伴有抑郁状态,这些情况可能严重影响其生活质量(QoL)和用药依从性。本研究旨在阐明抑郁与小细胞肺癌(SCLC)患者预后之间的复杂联系,并探讨其潜在机制。纳入186例新诊断为III期或IV期SCLC并接受铂类化疗的患者。在化疗开始前一天完成自评抑郁量表(SDS)问卷,以评估患者的抑郁状态。IV期SCLC患者或BMI较低者抑郁得分较高。在化疗不良反应方面,抑郁严重降低患者对化疗的耐受性及其QoL评分(R2 = 0.2385),还与严重呕吐(P < 0.001)、白细胞减少(R2 = 0.2332)和住院时间延长(R2 = 0.1961)相关。更重要的是,严重抑郁会降低患者的无进展生存期(PFS,R2 = 0.1943)和总生存期(OS,P < 0.01)。我们发现,严重抑郁患者血清BDNF水平下调,且血清BDNF水平与患者的OS高度相关(R2 = 0.2292)。通过体外MTT细胞活力测定,我们观察到BDNF联合处理明显增强了NCI-H69肿瘤细胞对顺铂的化疗敏感性,并诱导ABCG2表达下调。基于这些证据,抑郁与SCLC预后之间似乎确实存在关联,且抑郁影响预后的机制是通过下调BDNF表达实现的。

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