Breast carcinomas fulfill the Warburg hypothesis and provide metabolic markers of cancer prognosis
Breast carcinomas fulfill the Warburg hypothesis and provide metabolic markers of cancer prognosis
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DOI：
10.1093/carcin/bgi188
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发表时间：
2005-12-01
期刊：
影响因子：
4.7
通讯作者：
Cuezva, JM
中科院分区：
文献类型：
--
作者：
Isidoro, A;Casado, E;Cuezva, JM
这项研究的目的是研究乳腺癌代谢表型的选定蛋白质组学标志物，作为癌症进展的预后标志物。为此，检查了一系列的101个乳腺癌和13个未参考的乳房样品，以确定线粒体和糖酵解标记的蛋白质表达的定量差异。线粒体H+-ATP合酶（β-F1-ATPase）和热激蛋白60（HSP60）以及糖酵解甘油醛-3-磷酸脱氢酶，丙酮酸激酶，丙酸糖基酶和乳酸脱氢酶是通过免疫学技术鉴定的。通过肿瘤的临床病理信息和患者的随访数据，建立了蛋白质标志物表达水平的相关性和从中获得的比率的相关性。与正常样品相比，乳腺癌标本的代谢蛋白质组显示出明显的转变，同时朝着增强的糖酵解表型，同时发生的，对线粒体β-F1-ATPase/HSP60比率发生了深刻的变化。使用代谢特征的标记作为预测变量的判别分析表明，分类敏感性与97％相似。 Kaplan-Meier生存分析表明，一些蛋白质组学变量与患者的整体和无疾病生存显着相关。 Beta-F1-ATPase的表达水平本身允许鉴定预后明显较差的乳腺癌患者。多元COX回归分析表明，Beta-F1-ATPase的肿瘤表达是与临床变量无关的重要标记，可以评估患者的预后。我们得出的结论是，线粒体和糖酵解蛋白质组的改变是乳腺癌的标志性特征，进一步提供相关标记，以帮助乳腺癌患者的预后。
The aim of this study was to investigate selected proteomic markers of the metabolic phenotype of breast carcinomas as prognostic markers of cancer progression. For this purpose, a series of 101 breast carcinomas and 13 uninvolved breast samples were examined for quantitative differences in protein expression of mitochondrial and glycolytic markers. The beta-subunit of the mitochondrial H+-ATP synthase (beta-F1-ATPase) and heat shock protein 60 (Hsp60), and the glycolytic glyceraldehyde-3-phosphate dehydrogenase, pyruvate kinase and lactate dehydrogenase were identified by immunological techniques. Correlations of the expression level of the protein markers and of the ratios derived from them were established with the clinicopathological information of the tumors and the follow-up data of the patients. The metabolic proteome of breast cancer specimens revealed a pronounced shift towards an enhanced glycolytic phenotype concurrent with a profound alteration on the mitochondrial beta-F1-ATPase/Hsp60 ratio when compared with normal samples. Discriminant analysis using markers of the metabolic signature as predictor variables revealed a classification sensitivity of similar to 97%. Kaplan-Meier survival analysis showed that several of the proteomic variables significantly correlated with overall and disease-free survival of the patients. The expression level of beta-F1-ATPase per se allowed the identification of a subgroup of breast cancer patients with significantly worse prognosis. Multivariate Cox regression analysis indicated that tumor expression of beta-F1-ATPase is a significant marker independent from clinical variables to assess the prognosis of the patients. We conclude that the alteration of the mitochondrial and glycolytic proteomes is a hallmark feature of breast cancer further providing relevant markers to aid in the prognosis of breast cancer patients.