Heterogeneity of tumor-induced gene expression changes in the human metabolic network

Reprogramming of cellular metabolism is an emerging hallmark of neoplastic transformation. However, it is not known how metabolic gene expression 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., up-regulation of nucleotide biosynthesis and glycolysis) are frequently observed across tumors, expression changes of other pathways (e.g., oxidative phosphorylation and the tricarboxylic acid (TCA) cycle) are very heterogeneous. Our analysis also suggests that the expression changes of major metabolic processes across tumors can be rationalized in terms of several principal components. 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.