ArticleJournal of translational medicine2025
Multi-omics profiling reveals downregulated tumor lysine metabolism reshaping the immune microenvironment and therapeutic responses in hepatocellular carcinoma.
Article in Journal of translational medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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Who cites it
3 citing papers in PubMed.
- [Research progress on poor response, resistance mechanisms, and influencing factors of immunotherapy for hepatocellular carcinoma].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2026Review
- Beyond Glucose and Lipids: The Pivotal Role of Amino Acid Reprogramming in Shaping the Tumor Microenvironment and Guiding the Development of Novel Therapeutics.International journal of medical sciences · 2026Review
- Advances in the application of multi-omics in tumor immunotherapy.Frontiers in genetics · 2026Review
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11 authors.
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Abstract
backgroundHepatocellular carcinoma (HCC) is a major global health challenge with high aggressiveness and recurrence rates. Metabolic reprogramming is a cancer hallmark, enabling tumor cells to sustain rapid growth and evade immune surveillance. Several amino acids have been found to undergo metabolic reprogramming in tumors, and thus are potential anti-tumor targets. However, the characterization and implication of lysine metabolic reprogramming in HCC remain largely unexplored.
methodsWe performed multi-omics profiling, including transcriptomics, proteomics, single-cell omics, immunohistochemistry, and multiplex immunofluorescence on tumor and adjacent normal tissues obtained from 30 HCC patients. Integrative analyses and quantitative evaluations were carried out to characterize the lysine metabolism and investigate its implications for tumor progression, immune microenvironment, and immunotherapy responses.
resultsOur analysis observed a significant downregulation of lysine metabolism in HCC, with inter-patient heterogeneity. Patients with low lysine metabolism in tumors exhibited worse prognoses and a predominance of immunosuppressive tumor immune microenvironment (TIME), characterized by increased infiltration of myeloid-derived suppressor cells (MDSCs), regulatory T cells (Tregs), and exhausted CD8
conclusionsThis study provides comprehensive evidence that lysine metabolism plays a critical role in shaping the immunosuppressive TIME in HCC and is associated with clinical outcomes and resistance to immunotherapy, offering new insights into clinical molecular subtyping and potential therapeutic strategies.
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