The bioenergetic signature of lung adenocarcinomas is a molecular marker of cancer diagnosis and prognosis
The bioenergetic signature of lung adenocarcinomas is a molecular marker of cancer diagnosis and prognosis
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DOI：
10.1093/carcin/bgh113
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发表时间：
2004-07-01
期刊：
影响因子：
4.7
通讯作者：
Beer, DG
中科院分区：
文献类型：
--
作者：
Cuezva, JM;Chen, GA;Beer, DG
本研究的目的是研究肺腺癌的线粒体生物能量特征作为癌症进展的预后标志物。为了这个目的，一系列的90个肺腺癌和10个未涉及的肺样本进行了研究，蛋白质表达的定量差异，使用二维聚丙烯酰胺凝胶电泳。线粒体H+-ATP合酶（β-F1-ATP酶）和热休克蛋白60（Hsp 60）的β亚基，以及用于定义生物能细胞（BEC）指数的糖酵解甘油醛-3-磷酸脱氢酶（GAPDH），使用质谱和特异性抗体进行鉴定。并与肿瘤的临床病理资料及随访资料进行相关性分析。β-F1-ATP酶的表达在肺腺癌中显著降低，而Hsp 60和主要GAPDH同种型的表达没有显著变化。以β-F1-ATPase/Hsp 60比值和GAPDH表达作为预测变量的交叉验证分析显示分类敏感性为97.3%。高分化和细支气管肺泡肿瘤中β-F1-ATP酶/Hsp 60比值明显高于中、低分化和支气管来源的肿瘤。T1期肿瘤的BEC指数明显高于T2期肿瘤。同样，IA期肿瘤具有比IB期肿瘤更高的BEC指数。Kaplan-Meier生存分析显示，在相同大小或I期或无淋巴结转移（N 0）的肿瘤中，BEC指数低的患者预后明显较差。我们的结论是，肺腺癌的生物能量签名被改变，进一步提供了一个相关的标志物，肺腺癌的诊断和分类，并为肺癌患者的预后。
The aim of this study was to investigate the mitochondrial bioenergetic signature of lung adenocarcinomas as a prognostic marker of cancer progression. For this purpose, a series of 90 lung adenocarcinomas and 10 uninvolved lung samples were examined for quantitative differences in protein expression using two-dimensional polyacrylamide gel electrophoresis. The beta subunit of the mitochondrial H+-ATP synthase (beta-F1-ATPase) and heat shock protein 60 (Hsp 60), and the glycolytic glyceraldehyde-3-phosphate dehydrogenase (GAPDH), used to define the bioenergetic cellular (BEC) index, were identified using mass spectrometry and specific antibodies. Correlations of the expression level of the protein markers and of the BEC index were established with the clinicopathological information of the tumors and the follow-up data of the patients. The expression of beta-F1-ATPase is significantly reduced in lung adenocarcinomas in the absence of significant changes in the expression of Hsp 60 and of a major GAPDH isoform. Cross-validation analysis using the beta-F1-ATPase/Hsp 60 ratio and GAPDH expression as predictor variables revealed a classification sensitivity of 97.3%. The beta-F1-ATPase/Hsp 60 ratio is significantly higher in well differentiated and bronchioloalveolar tumors than in moderate or poorly differentiated and in bronchial-derived tumors. The BEC index of T1 tumors was significantly higher than that of T2 tumors. Likewise, stage IA tumors had a higher BEC index than stage IB tumors. Kaplan-Meier survival analysis using the BEC index as predictor of survival revealed that within tumors of the same size or stage I or with no lymph node metastasis (N0) the patients bearing 'low' BEC index tumors had a significant worse prognosis. We conclude that the bioenergetic signature of lung adenocarcinomas is altered, further providing a relevant marker for the diagnosis and classification of lung adenocarcinomas, and for the prognosis of lung cancer patients.