Genetic Signature of Down-Regulated Oxidative Phosphorylation (OXPHOS) Genes Associated with Poor Prognosis in Cancer

Researchers from the Medical Research Council (MRC) Cancer Unit at the University of Cambridge (UK) have identified a genetic signature related to metabolism that is associated with poor patient prognosis. The results of the analysis of 8,161 tissue samples could in the future help clinicians decide how best to treat a patient as well as aid the development of new targeted treatments. For cancer cells to grow and spread they undergo a complex metabolic transformation. This allows the cells to meet the energy needs for the cancer to proliferate. Increasing our understanding of the genes that underpin the changes to metabolic pathways will provide further insight into the events that lead to the spread of cancer within the body. To this end, Dr. Christian Frezza, program leader, and Edoardo Gaude, a Ph.D. student, from the MRC Cancer Unit, analyzed the expression of metabolic genes across 20 different solid cancer types from 8,161 tumor and non-cancerous samples held in The Cancer Genome Atlas (TCGA). The researchers found that genes related to the oxidative phosphorylation (OXPHOS) pathway--a metabolic pathway in the cell's mitochondria that provides energy to the cell--were significantly down-regulated in the tumor cells from patients with poor clinical outcome. Furthermore, suppression of OXPHOS genes was linked to metastasis, where the cancer spreads to other parts of the body and is linked to even poorer prognosis. “We find that cancers undergo a tissue-specific metabolic rewiring, which converges towards a common metabolic landscape. Of note, downregulation of mitochondrial genes is associated with the worst clinical outcome across all cancer types and correlates with the expression of epithelial-to-mesenchymal transition gene signature, a feature of invasive and metastatic cancers,” the authors wrote.
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