Serum Molecular Signatures of Weight Change during Early Breast Cancer Chemotherapy
Serum Molecular Signatures of Weight Change during Early Breast Cancer Chemotherapy
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DOI：
10.1158/1078-0432.ccr-09-1452
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发表时间：
2009-11-01
影响因子：
11.5
通讯作者：
Stebbing, Justin
中科院分区：
文献类型：
--
作者：
Keun, Hector C.;Sidhu, Jasmin;Stebbing, Justin
目的：接受乳腺癌化疗的女性体重增加与较高的复发风险相关，但其机制尚不清楚。实验设计：为了研究这一点，我们评估了绝经后女性早期乳腺癌辅助化疗期间代谢、细胞因子和食欲相关肽的变化，并将这些与体重测量相关联。具体来说，我们使用连续血清的 H-1 核磁共振波谱进行了整体代谢分析，检查了生长素释放肽免疫反应性、GLP-1 和肽 YY 的 RIA，以及对连续样本进行电化学发光细胞因子分析（肿瘤坏死因子-a 和白介素-6）。结果：在体重增加 >1.5 公斤的患者中，多种代谢物水平与体重增加呈正相关，特别是乳酸，在体重增加的患者中，乳酸水平增加了 63.5%。与体重未增加的患者相比，化疗期间体重增加（P < 0.01；预先设定的主要终点）。体重变化率与血清乳酸水平之间存在很强的相关性（r = 0.7，P < 0.001），平均而言，乳酸水平对化疗表现出最大的代谢反应，增加高达 75%。在治疗后体重未增加的患者中，还观察到肽 YY 的标准化水平升高（与体重增加组的 -7% 相比，+30%；p < 10(-4)）。基线乳酸、丙氨酸和体脂均是体重增加的预后指标（受试者工作特征曲线下面积，>0.77；P < 0.05）。没有观察到任何其他参数和体重增加（包括细胞因子水平）之间的关联。结论：代谢组学识别了乳腺癌化疗期间扰乱的过量能量消耗途径，并建立了化疗期间血清乳酸、体脂肪和实质性体重增加之间的显着关联。 (临床癌症研究 2009;15(21):6716-23)
Purpose: Weight gain in women receiving chemotherapy for breast cancer is associated with a higher risk of recurrence but its mechanisms are poorly understood.Experimental Design: To investigate this, we assessed the metabolic, cytokine, and appetite-related peptide alterations during adjuvant chemotherapy for early breast cancer in postmenopausal women, and correlated these with body mass measurements. Specifically, we performed global metabolic profiling using H-1-nuclear magnetic resonance spectroscopy of sequential sera, examined ghrelin immunoreactivity, RIAs for GLP-1 and peptide YY, and electrochemiluminescent cytokine analyses (tumor necrosis factor-a and interleukin-6) on sequential samples.Results: In those who gained >1.5 kg, several metabolite levels were positively associated with weight gain, specifically lactate, which was 63.5% greater in patients with increased body weight during chemotherapy compared with those with no weight gain (P < 0.01; the prespecified primary end point). A strong correlation (r = 0.7, P < 0.001) was detected between the rate of weight change and serum lactate levels, and on average, lactate levels exhibited the greatest metabolic response to chemotherapy, increasing by up to 75%. Normalized levels of peptide YY were also observed to be elevated in patients not gaining weight posttreatment (+30% compared with -7% for the weight gain group; p < 10(-4)). Baseline lactate, alanine, and body fat were all prognostic for weight gain (area under the receiver operator characteristic curves, >0.77; P < 0.05). No associations were observed between any other parameter and weight gain, including cytokine levels.Conclusions: Metabonomics identifies excess energy expenditure pathways perturbed during chemotherapy for breast cancer, and establishes a significant association between serum lactate, body fat, and substantive weight gain during chemotherapy. (Clin Cancer Res 2009;15(21):6716-23)