Purine metabolism: a pan-cancer metabolic dysregulation across circulation and tissues

Tumors function as organ-like entities within complex ecosystems, interacting with diverse components of their microenvironment, including blood and lymphatic vessels, neurons, immune cells, metabolites, and cytokines, to drive tumorigenesis and progression. Our pan-cancer study investigated the universal tumor hallmarks, integrating metabolite characteristics with molecular mechanisms. Metabolomic profiling on plasma from 2,561 patients across 20 cancer types and 604 healthy controls in two clinical centers, identified three biomarkers in pan cancers: elevated levels of hypoxanthine and reduced levels of cysteine and pyruvic acid. Given the profound significance of hypoxanthine, we further discovered 33 core purine metabolism-related genes in The Cancer Genome Atlas (TCGA) pan-cancer tissues, and their influences on immunomodulation and overall survival. Lastly, candidate therapeutic compounds, intervening purine metabolism, were proposed based on pharmaco-transcriptomics and pharmaco-proteomics analysis. Through interdisciplinary multi-omics investigations, such approaches may enhance insight into antitumor immunotherapy by targeting cancer metabolic reprogramming.