Isocitrate Dehydrogenase: Three Subunits in Different Cancer Types—Changes in Gene Expression, Mutation Status, and Cancer Progression.

The isocitrate dehydrogenase (IDH) gene encodes three protein isoforms (IDH1, IDH2 and IDH3). IDH3 exists in three subunits (IDH3A, IDH3B, and IDH3G). Examining the gene expression level and mutation status of IDH3 subunits could help find new diagnoses or treatment options for specific cancer types. Until now, studies on the IDH3 enzyme have been focused on the IDH3A subunit and a few types of cancer. In our study, the effect of IDH3A, IDH3B, and IDH3G expression changes on cancer progression and survival in the ten major cancer types were investigated using bioinformatic tools. Then, the impact of mutation status on cancer progression was examined in the TCGA database. The expression level of IDH3 subunits increased as the bladder, breast, colon, esophageal, lung, and stomach cancers progressed. The elevated expression level of all IDH3 subunit expressions leads to poor prognosis in colon, esophageal, lung, prostate, and stomach cancers. The cumulative alteration rates revealed low-frequency (0.3-5.9 %) mutations in all IDH3 subunits. IDH3A, IDH3B, and IDH3G expression was significantly altered after mutation among all types of cancer studied except the prostate. Our data showed that there may be correlation between the mutation status of the IDH3 subunits and breast, esophageal, lung and stomach cancer progression.