Elevated IL-8, TNF-α, and MCP-1 in men with metastatic prostate cancer starting androgen-deprivation therapy (ADT) are associated with shorter time to castration-resistance and overall survival
Elevated IL-8, TNF-α, and MCP-1 in men with metastatic prostate cancer starting androgen-deprivation therapy (ADT) are associated with shorter time to castration-resistance and overall survival
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DOI：
10.1002/pros.22788
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发表时间：
2014-06-01
期刊：
影响因子：
2.8
通讯作者：
Sweeney, Christopher J.
中科院分区：
文献类型：
--
作者：
Sharma, Jaya;Gray, Kathryn P.;Sweeney, Christopher J.
背景：趋化因子和细胞因子与去势耐受前列腺癌(CRPC)的进展有关。方法收集122名男性患者的前瞻性数据，这些患者在接受ADT治疗转移性前列腺癌后的中位数为0.5个月。采用多重电化学发光法测定MCP-1、IL-1-β、IL-2、IL-8、IL-6和TNF-α水平。多变量COX模型通过蛋白水平评估了时间与CRPC和总生存率的关系，并根据临床变量(ADT开始时的年龄和前列腺特异性抗原(PSA)水平、种族、ECOG状态和转移程度)进行了调整。风险比(HR)与95%可信区间(CI)相关。结果中位随访时间为44个月，总生存期为42.2个月。ECOG功能状态与总生存期呈负相关[HR=2.8(1.1~7.0)，P=0.0 3]，PSA最低值0.2预示慢性前列腺癌发生的时间较长[HR=0.3(0.2~0.5)，P<；0.0001]。白介素8、肿瘤坏死因子-α、单核细胞趋化蛋白-1达到CRPC的HR分别为1.4(95%CI：0.9，2.2，P=0.13)、1.3(95%CI：0.8，2，P=0.18)和1.0(95%CI：0.7，1.6，P=0.95)。蛋白水平高于中位数的患者总生存率分别为：IL-8 1.9(95%CI：1.0，3.5，P=0.04)；TNF-α2.0(95%CI：1.1，3.5，P=0.02)；MCP-1 1.7(95%CI：1.7，3.0，P=0.08)。与IL-1-β、IL-2或IL-6无关。结论：炎症相关细胞因子水平越高，前列腺癌预后越差，可能指导改善前列腺癌治疗的策略。前列腺癌74：820-828,2014。(C)2014年威利期刊公司。
BACKGROUNDChemokines and cytokines have been implicated in progression to castration-resistant prostate cancer (CRPC).METHODSRetrospective data were accessed from 122 men with serum samples drawn at a median of 0.5 months after starting ADT for metastatic prostate cancer. MCP-1, IL-1-beta, IL-2, IL-8, IL-6, and TNF-alpha levels were measured by multiplex electrochemiluminescence assays. A multivariable Cox model assessed the association of time to CRPC and overall survival by the protein levels and adjusted for clinical variables (age and prostate specific antigen (PSA) levels at start of ADT, race, ECOG status, and extent of metastases). Associations were reported as hazard ratio (HR) with 95% confidence interval (CI).RESULTSMedian follow-up and overall survival were 44 and 42.2 months, respectively. ECOG performance status (>= 1 vs. 0) was negatively associated with overall survival [HR = 2.8 (1.1-7.0), P = 0.03], and PSA nadir < 0.2 was predictive of longer time to development of CRPC [HR = 0.3 (0.2-0.5), P < 0.0001]. The HR for time to CRPC by protein above the median was 1.4 (95% CI: 0.9, 2.2, P = 0.13) for IL-8; 1.3 (95% CI: 0.8, 2, P = 0.18) for TNF-alpha; 1.0 (95% CI: 0.7, 1.6, P = 0.95) for MCP-1. The HR for median overall survival for protein levels above the median was: 1.9 (95% CI: 1.0, 3.5, P = 0.04) for IL-8; 2.0 (95% CI: 1.1, 3.5, P = 0.02) for TNF-alpha; 1.7 (95% CI: 1.7, 3.0, P = 0.08) for MCP-1. There was no association with IL-1-beta, IL-2, or IL-6.CONCLUSIONHigher levels of inflammation-associated cytokines correlate with poorer prostate cancer outcomes and may guide strategies to improve prostate cancer therapy. Prostate 74:820-828, 2014. (c) 2014 Wiley Periodicals, Inc.