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

Cancer Gene Therapy volume 32, pages 1177–1190 (2025)Cite this article

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Abstract

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.

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Fig. 1: ST Reveals Spatial Heterogeneity in BC and Adjacent Tissues.
Fig. 2: The differential analysis of BC and adjacent tissues through the integration of ST and SM.
Fig. 3: Upregulation of Choline metabolism in BC tissues.
Fig. 4: In BC tissues, carbon metabolism, particularly the TCA cycle pathway, is upregulated.
Fig. 5: Downregulation of Sphingolipid Metabolism in BC Tissues.
Fig. 6: Downregulation of Tryptophan Metabolism in BC Tissues.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (Grant No. 82473955, 82173842), the Fundamental Research Funds for the Central Universities (2632025TD04), and the Priority Academic Program Development (PAPD) of Jiangsu Higher Education Institutions. We would like to thank the Wuhan Metware Biotechnology Co., Ltd. (Wuhan, China) for spatial multi-omics analysis.

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  1. These authors contributed equally: Yu Lu, Fangdie Ye.

Authors and Affiliations

  1. School of Life Science and Technology, China Pharmaceutical University, 639 Longmian Road, Nanjing, Jiangsu Province, China

    Yu Lu, Xuedan Han, Zihan Wang & Lufeng Zheng

  2. Department of Urology, Huashan Hospital, Fudan University, Shanghai, China

    Fangdie Ye

  3. Fudan Institute of Urology, Huashan Hospital, Fudan University, Shanghai, China

    Fangdie Ye

  4. Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province, China

    Xiaoman Li

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Contributions

Lufeng Zheng designed the research. Yu Lu, Fangdie Ye, Xuedan Han and Zihan Wang analyzed the data. Yu Lu and Fangdie Ye performed the research. Yu Lu and Fangdie Ye wrote the paper. Lufeng Zheng and Xiaoman Li reviewed this paper. All authors read and approved the final manuscript.

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Lu, Y., Ye, F., Han, X. et al. Integrated spatial transcriptome and metabolism study reveals metabolic heterogeneity in human bladder cancer. Cancer Gene Ther 32, 1177–1190 (2025). https://doi.org/10.1038/s41417-025-00947-z

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