RESULTS

Mathematical analysis predicts imbalanced IDH1/2 expression associates with 2-HG-inactivating pathway in colorectal cancer (Int J Oncol, 46, 1181-1191, 2014)

Bioinformatics and computational modeling offer innovative approaches to investigate cancer metabolism and predict the secondary and tertiary cellular responses. A significant proportion of patients with glioblastoma and hematological malignancies harbor the mutated forms of the oxidative phosphorylation (OxPhos) enzymes, isocitrate dehydrogenase (IDH) 1 or 2. The mutated forms of IDH1 and IDH2 produce an oncogenic metabolite, D-2-hydroxyglutarate (D2HG). We computationally analyzed gene expression in colorectal cancer (CRC), and identified novel sets of genes that are associated with patient survival. The study of OxPhos-related genes revealed that an imbalance between the expression of IDH1 and IDH2, defined as over expression of one isoform in relation to the other, was associated with worse prognosis in CRC patients. This effect was accentuated by reduced expression of the 2-HG-inactivating pathway. These findings suggest a yet uncharacterized mechanism to discover novel therapeutic targets for the treatment of CRC.