Fig. 7.

HCC tumors display antagonistic metabolic behavior associated with redox responses. Genes of ALDH2 and G6PD clusters (blue and red nodes) promoted several reactions and processes, as summarized at the bottom of the figure. Reducing equivalents (NADPH and NADH) are highlighted (black nodes). Dashed lines indicate regulatory processes. Genes in the G6PD and ALDH2 clusters (black-circled red and blue nodes) and some of their co-expressed genes (Fig. 4). The reaction catalyzed by H6PD occurred in the endoplasmic reticulum. Note the differences in ROS metabolism in tumors with high expression of ALDH2-clustered genes (blue) vs G6PD-clustered genes (red). Prdx5 was expressed by hALDH2 and hG6PD tumors, but mitochondrial ROS consumption by this gene was only active in hG6PD. Expression profiles of G6PD, HIF1A, PKM and MTHFS, genes in the two redox clusters, identified a signature that more effectively predicted patient survival than predictions from a single gene. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)