Depressive symptoms and cortisol rhythmicity predict survival in patients with renal cell carcinoma: role of inflammatory signaling.
Depressive symptoms and cortisol rhythmicity predict survival in patients with renal cell carcinoma: role of inflammatory signaling.
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DOI：
10.1371/journal.pone.0042324
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Pisters L
中科院分区：
文献类型：
--
作者：
Cohen L;Cole SW;Sood AK;Prinsloo S;Kirschbaum C;Arevalo JM;Jennings NB;Scott S;Vence L;Wei Q;Kentor D;Radvanyi L;Tannir N;Jonasch E;Tamboli P;Pisters L
有证据支持心理因素与癌症生物学之间的关联;然而，研究结果对心理社会因素在癌症进展中的作用是模棱两可的。本研究通过检查转移性肾细胞癌（RCC）患者的心理社会因素和皮质醇失调的临床影响，并检查相关的转录控制通路的激活，产生了一个假设的机制变量。转移性RCC患者（n = 217）前瞻性入组本研究。 患者完成问卷调查（流行病学研究中心-抑郁症; SF-36健康状况调查;杜克社会支持指数;应对操作偏好调查;有组织和无组织的宗教活动;和内在的宗教信仰），并提供血液和唾液样本。评估皮质醇水平和全基因组转录谱，以确定昼夜节律和基因组途径的潜在改变。控制疾病风险类别的单独考克斯回归模型显示，CES-D评分（p = 0.05，HR = 1.5，HR的95%CI：1.00-2.23）和皮质醇斜率（p = 0.002; HR = 1.9; HR的95%CI：1.27-2.97）与生存率降低显著相关。 只有皮质醇斜率和风险类别在完整模型中保持显著性。功能基因组分析将抑郁症状与循环白细胞中促炎和促转移基因的表达增加联系起来。在高CES-D患者中，发现116个转录本平均上调50%或更多，57个转录本下调至少50%。这些变化也在一部分患者的肿瘤中发现。这些发现确定抑郁症状是肾细胞癌患者生存的关键预测因子，并与皮质醇和炎症生物学失调有潜在联系。
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. 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. 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. 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.
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影响因子：
5.8
作者：
Cole, SW;Yan, W;Zack, JA
通讯作者：
Zack, JA
影响因子：
3.4
作者：
KOENIG, HG;WESTLUND, RE;HYBELS, C
通讯作者：
HYBELS, C
DOI：
10.1073/pnas.0911515107
发表时间：
2010-03-23
影响因子：
11.1
作者：
Cole, Steven W.;Arevalo, Jesusa M. G.;Seeman, Teresa E.
通讯作者：
Seeman, Teresa E.
影响因子：
3.3
作者：
Cohen, L;de Moor, C;Amato, RJ
通讯作者：
Amato, RJ
影响因子：
11.5
作者：
Lin, Yvonne G.;Kunnumakkara, Ajaikumar B.;Sood, Anil K.
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Sood, Anil K.