Center for Computational Biology and Bioinformatics and Initiative in Systems Biology, Columbia University, New York, New York, USA.
Nat Biotechnol. 2013 Jun;31(6):522-9. doi: 10.1038/nbt.2530. Epub 2013 Apr 21.
Reprogramming of cellular metabolism is an emerging hallmark of neoplastic transformation. However, it is not known how the expression of metabolic genes in tumors differs from that in normal tissues, or whether different tumor types exhibit similar metabolic changes. Here we compare expression patterns of metabolic genes across 22 diverse types of human tumors. Overall, the metabolic gene expression program in tumors is similar to that in the corresponding normal tissues. Although expression changes of some metabolic pathways (e.g., upregulation of nucleotide biosynthesis and glycolysis) are frequently observed across tumors, expression changes of other pathways (e.g., oxidative phosphorylation) are very heterogeneous. Our analysis also suggests that the expression changes of some metabolic genes (e.g., isocitrate dehydrogenase and fumarate hydratase) may enhance or mimic the effects of recurrent mutations in tumors. On the level of individual biochemical reactions, many hundreds of metabolic isoenzymes show significant and tumor-specific expression changes. These isoenzymes are potential targets for anticancer therapy.
细胞代谢的重编程是肿瘤发生的一个新兴标志。然而，目前尚不清楚肿瘤中代谢基因的表达与正常组织有何不同，也不知道不同类型的肿瘤是否表现出相似的代谢变化。在这里，我们比较了 22 种不同类型的人类肿瘤中代谢基因的表达模式。总的来说，肿瘤中的代谢基因表达谱与相应的正常组织相似。尽管一些代谢途径（如核苷酸生物合成和糖酵解的上调）的表达变化在肿瘤中经常观察到，但其他途径（如氧化磷酸化）的表达变化则非常多样化。我们的分析还表明，一些代谢基因（如异柠檬酸脱氢酶和延胡索酸水合酶）的表达变化可能增强或模拟肿瘤中反复出现的突变的作用。在单个生化反应的水平上，有数百种代谢同工酶表现出显著的、肿瘤特异性的表达变化。这些同工酶是癌症治疗的潜在靶点。
