Integrated spatial transcriptome and metabolism study reveals metabolic heterogeneity in human bladder cancer

Bladder cancer (BC) is a malignancy that originates from the cells lining the bladder and is one of the most common cancers of the urinary system, capable of occurring in any part of the bladder. However, the molecular mechanisms underlying the malignant transformation of BC have not been systematically studied. This study integrated cutting-edge techniques of spatial transcriptomics (ST) and spatial metabolomics (SM) to capture the transcriptomic and metabolomic landscapes of both BC and adjacent normal tissues. ST results revealed a significant upregulation of genes associated with choline metabolism and glucose metabolism, while genes related to sphingolipid metabolism and tryptophan metabolism were significantly downregulated. Additionally, significant metabolic reprogramming was observed in BC tissues, including the upregulation of choline metabolism and glucose metabolism, as well as the downregulation of sphingolipid metabolism and tryptophan metabolism. These alterations may play a crucial role in promoting tumorigenesis and immune evasion of BC. The interpretation of ST and SM data in this study offers new insights into the molecular mechanisms underlying BC progression and provides valuable clues for the prevention and treatment of BC. Schematic illustration of BC metabolic reprogramming.