Concordant release of glycolysis proteins into the plasma preceding a diagnosis of ER+ breast cancer.
Concordant release of glycolysis proteins into the plasma preceding a diagnosis of ER+ breast cancer.
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DOI：
10.1158/0008-5472.can-11-3266
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发表时间：
2012-04-15
期刊：
影响因子：
11.2
通讯作者：
Hanash SM
中科院分区：
文献类型：
--
作者：
Amon LM;Pitteri SJ;Li CI;McIntosh M;Ladd JJ;Disis M;Porter P;Wong CH;Zhang Q;Lampe P;Prentice RL;Hanash SM
虽然外周血生物标志物的鉴定将增强乳腺癌的早期检测策略，但蛋白质标志物的发现一直具有挑战性。在这项研究中，我们试图确定协调变化的血浆蛋白与乳腺癌的基础上大规模定量质谱。我们分析了从420例ER+病例和妇女健康倡议队列中登记的匹配对照中收集的诊断前74周的血浆样本。基因集富集分析应用于467个定量蛋白质，将其相应的基因与特定的生物学途径联系起来。基于个体蛋白质浓度的差异，糖酵解途径蛋白质在病例和对照之间表现出统计学显著差异。特别是，在接近诊断时抽血的病例中观察到富集（0-38周诊断前组的效应量：1.91; p值：8.3E-05）。在诊断时从一组独立的病例和对照组收集的血浆分析证实了病例相对于对照组的糖酵解蛋白水平上调。总之，我们的研究结果表明，糖酵解蛋白的伴随释放到血浆中是一个病理生理事件，ER+乳腺癌的诊断之前。
Although the identification of peripheral blood biomarkers would enhance early detection strategies for breast cancer, the discovery of protein markers has been challenging. In this study, we sought to identify coordinated changes in plasma proteins associated with breast cancer based on large scale quantitative mass spectrometry. We analyzed plasma samples collected up to 74 weeks prior to diagnosis from 420 ER+ cases and matched controls enrolled in the Women's Health Initiative cohort. A gene set enrichment analysis was applied to 467 quantified proteins linking their corresponding genes to particular biological pathways. Based upon differences in the concentration of individual proteins, glycolysis pathway proteins exhibited a statistically significant difference between cases and controls. In particular, the enrichment was observed among cases in which blood was drawn closer to diagnosis (effect size for the 0–38 weeks pre-diagnostic group: 1.91; p-value: 8.3E-05). Analysis of plasmas collected at the time of diagnosis from an independent set of cases and controls confirmed upregulated levels of glycolysis proteins among cases relative to controls. Together, our findings indicate that the concomitant release of glycolysis proteins into the plasma is a pathophysiological event that precedes a diagnosis of ER+ breast cancer.