Plasma growth differentiation factor 15 is associated with weight loss and mortality in cancer patients.
Plasma growth differentiation factor 15 is associated with weight loss and mortality in cancer patients.
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DOI：
10.1002/jcsm.12033
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发表时间：
2015-12
期刊：
影响因子：
--
通讯作者：
Garcia JM
中科院分区：
文献类型：
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作者：
Lerner L;Hayes TG;Tao N;Krieger B;Feng B;Wu Z;Nicoletti R;Chiu MI;Gyuris J;Garcia JM
癌症相关的体重减轻与炎症增加和生存率降低有关。新型炎症介质生长分化因子（GDF）15与癌症预后不良相关，但其在癌症相关性体重减轻（C-WL）中的作用尚不清楚。我们的目的是测量癌症受试者和对照组血浆样本中的GDF15，并确定其与其他炎症标志物和临床结果的关联。我们测量了与癌症相关体重减轻的男性（C-WL, n = 58）、体重稳定的癌症患者（C-WS, n = 72）和非癌症对照组（Co, n = 59）的体重、食欲、血浆GDF15和其他炎症标志物，这些患者与年龄和病前体重指数相匹配。在一部分患者中，我们还测量了握力、阑尾瘦体重（aLBM）、东部肿瘤合作组（ECOG）和Karnofsky表现评分。与其他组相比，C-WL组GDF15、白细胞介素(IL)-6、IL-8升高。白细胞介素-1受体拮抗剂、白细胞介素-4、干扰素- γ、肿瘤坏死因子α和血管内皮生长因子A在C-WL组与C-WS组相比升高，激活素A在Co组与其他组相比显著下调。C-WL患者的握力、aLBM和脂肪量较低，东部肿瘤合作组和Karnofsky表现评分在两个癌症组中均较低。GDF15、IL-6、IL-8与体重减轻显著相关；GDF15与aLBM、握力和脂肪量呈负相关。IL-8和激活素A与aLBM和脂肪量呈负相关。GDF15和IL-8预测了调整分期和体重变化后的生存（两者的Cox回归P < 0.001）。GDF15和其他炎症标志物与癌症患者体重减轻、aLBM和力量下降以及生存率差有关。GDF15可以作为癌症患者的预后指标，并被评估为癌症相关减肥的潜在治疗靶点。
Cancer-related weight loss is associated with increased inflammation and decreased survival. The novel inflammatory mediator growth differentiation factor (GDF)15 is associated with poor prognosis in cancer but its role in cancer-related weight loss (C-WL) remains unclear. Our objective was to measure GDF15 in plasma samples of cancer subjects and controls and establish its association with other inflammatory markers and clinical outcomes. We measured body weight, appetite, plasma GDF15, and other inflammatory markers in men with cancer-related weight loss (C-WL, n = 58), weight stable patients with cancer (C-WS, n = 72), and non-cancer controls (Co, n = 59) matched by age and pre-illness body mass index. In a subset of patients we also measured handgrip strength, appendicular lean body mass (aLBM), Eastern Cooperative Oncology Group (ECOG), and Karnofsky performance scores. GDF15, interleukin (IL)-6 and IL-8 were increased in C-WL versus other groups. IL-1 receptor antagonist, IL-4, interferon–gamma, tumour necrosis factor alpha, and vascular endothelial growth factor A were increased in C-WL versus C-WS, and Activin A was significantly downregulated in Co versus other groups. C-WL patients had lower handgrip strength, aLBM, and fat mass, and Eastern Cooperative Oncology Group and Karnofsky performance scores were lower in both cancer groups. GDF15, IL-6, and IL-8 significantly correlated with weight loss; GDF15 negatively correlated with aLBM, handgrip strength, and fat mass. IL-8 and Activin A negatively correlated with aLBM and fat mass. GDF15 and IL-8 predicted survival adjusting for stage and weight change (Cox regression P < 0.001 for both). GDF15 and other inflammatory markers are associated with weight loss, decreased aLBM and strength, and poor survival in patients with cancer. GDF15 may serve as a prognostic indicator in cancer patients and is being evaluated as a potential therapeutic target for cancer-related weight loss.