Tissue-specific and convergent metabolic transformation of cancer correlates with metastatic potential and patient survival

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Abstract

Cancer cells undergo a multifaceted rewiring of cellular metabolism to support their biosynthetic needs. Although the major determinants of this metabolic transformation have been elucidated, their broad biological implications and clinical relevance are unclear. Here we systematically analyse the expression of metabolic genes across 20 different cancer types and investigate their impact on clinical outcome. 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. Consistently, suppression of mitochondrial genes is identified as a key metabolic signature of metastatic melanoma and renal cancer, and metastatic cell lines. This comprehensive analysis reveals unexpected facets of cancer metabolism, with important implications for cancer patients' stratification, prognosis and therapy.

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