PLoS ONE：炎症基因表达调控或导致抑郁症与癌症患者存活率的相关性

根据一项新的研究证实：抑郁症症状与癌症患者的生存时间较短相关。近日，得克萨斯大学MD安德森癌症中心研究人员在8月1日的PLoS ONE杂志上发表论文称：这种相关性可能是由于应激激素调节异常和炎症基因表达导致的。

肿瘤学和行为科学中心部门教授Lorenzo Cohen说：研究发现心理健康和社会福祉良好是可以影响生物过程以及影响癌症发展的。该研究还表明，心理健康筛查应该是标准治疗的一部分，因为这是公认的可以帮助人们管理困扰的方法，即使在面对危及生命疾病的情况下。

在研究中，研究人员分析了超过217例新诊断肾细胞癌已经扩散五年的患者。参与人员回答了研究者的宗教和精神问题。他们还询问了他们的抑郁症症状、生活质量和应对技能等。患者也提供了血液样本，以及5个唾液样本，每天一次共三天。

研究人员使用唾液样本来跟踪患者的皮质醇、应激激素的全天变化情况，发现通常是在早晨高，之后会下降。在跟踪分析时，64％的患者已经死亡。这些患者被确诊后存活的平均时间为1.8年。

总的来说这项研究表明，23％的患者存在临床抑郁症。即使考虑其他疾病相关的危险因素后，研究者指出，抑郁症也是会导致存活时间较短。此外，研究表明体内皮质醇水平全天都高于正常水平也会降低癌症患者的生存。

使用15例存在抑郁症最显著的症状患者与抑郁症最温和患者的15个组织样本，研究人员进行全基因组分析，以确定是否忧郁症与癌症死亡的风险增加有关。他们发现调节细胞炎症的特定信号通路在抑郁症癌症患者表达水平明显提高，在这种相关性中起到了关键作用。

这项研究的作者得出结论：患者的心理健康和生存时间之间的联系与炎症基因表达调控相关。研究结果表明，现在能够确定一些可能的机理来解释抑郁症和生存之间的关联。虽然这项研究发现抑郁症和癌症存活率之间的关联，但它并不能证明两者之间的因果关系。

doi:10.1371/journal.pone.0042324
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Depressive Symptoms and Cortisol Rhythmicity Predict Survival in Patients with Renal Cell Carcinoma: Role of Inflammatory Signaling

Lorenzo Cohen1*, Steven W. Cole2, Anil K. Sood3, Sarah Prinsloo1, Clemens Kirschbaum4, Jesusa M. G. Arevalo2, et al.

Purpose

Evidence has supported the association between psychological factors and cancer biology; however, findings are equivocal on the role of psychosocial factors in cancer progression. This study generates a hypothesis of mechanistic variables by examining the clinical effects of psychosocial factors and cortisol dysregulation in patients with metastatic renal cell carcinoma (RCC) and examines associated activation of transcription control pathways.

Methods

Patients with metastatic RCC (n = 217) were prospectively enrolled in this study. Patients completed questionnaires (Centers for Epidemiologic Studies – Depression; SF-36 Health Status Survey; Duke Social Support Index; Coping Operations Preference Enquiry; organized and non-organized religious activity; and intrinsic religiosity), and provided blood and saliva samples. Cortisol levels and whole genome transcriptional profiling were assessed to identify potential alterations in circadian rhythms and genomic pathways.

Results

Separate Cox regression models, controlling for disease risk category, revealed that CES-D scores (p = 0.05, HR = 1.5, 95% CI for HR: 1.00–2.23) and cortisol slope (p = 0.002; HR = 1.9; 95%CI for HR: 1.27–2.97) were significantly associated with decreased survival. Only cortisol slope and risk category remained significant in the complete model. Functional genomic analyses linked depressive symptoms to increased expression of pro-inflammatory and pro-metastatic genes in circulating leukocytes. 116 transcripts were found to be upregulated by an average of 50% or more in high CES-D patients, and 57 transcripts downregulated by at least 50%. These changes were also found in the tumor in a subset of patients.

Conclusion

These findings identify depressive symptoms as a key predictor of survival in renal cell carcinoma patients with potential links to dysregulation of cortisol and inflammatory biology.