Integrated Gene Coexpression Network And Metabolic Network Prediction Of New Cancer Targets And Potential Anticancer Drugs

Metabolic alterations and adaptations are critical for cancer cell transformation and progression. In this study, we exploited cancer cell metabolism by integrating the cancer gene co-expression network with the metabolic network constructed by linking enzymes with shared metabolites. Through the cancer gene co-expression network, we identified gene co-expression modules that are significantly up or down regulated in cancer cells. By focusing on the cancer-specific gene co-expression modules, we identified key enzyme-coding genes that are co-expressed with unexpected more number of metabolite-sharing enzyme-coding genes inside the module. We hypothesize that alterations of such enzyme-coding genes or their corresponding metabolites may have a great impact on cancer cell metabolism. Accordingly, these genes and their associated metabolites may serve as potential drug targets and drugs for cancer treatments. We applied this approach, named Met-express, to lung cancer, leukaemia and breast cancer, and predicted a number of key enzyme-coding genes and metabolites for each cancer. Database comparison and a literature search revealed that around20-30%of the identified key enzyme-coding genes have been either used as the anti-cancer drug targets or suggested to become novel anti-cancer drug targets. Four out of50predicted metabolites present in all three types of cancer have already been approved for cancer therapy, with a significant fraction of the predicted metabolites suggested to have cancer therapeutic effects. As such, the integrated approach not only is useful in identifying the key components in cancer cell metabolism, but also provides a general platform for studying the metabolism of other diseases.