Heterogeneity in polyamine metabolism dictates prognosis and immune checkpoint blockade response in hepatocellular carcinoma
Immune checkpoint blockade holds promise in hepatocellular carcinoma (HCC) treatment, but its efficacy remains limited. Dysregulated polyamine metabolism and its interaction with oncogenic pathways promote tumor progression. However, the heterogeneity of polyamine metabolism and its effects on the i...
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Frontiers Media S.A.
2025-02-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1516332/full |
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| author | Jianyan Pan Zhong Lin Qinchun Pan Tao Zhu |
| author_facet | Jianyan Pan Zhong Lin Qinchun Pan Tao Zhu |
| author_sort | Jianyan Pan |
| collection | DOAJ |
| description | Immune checkpoint blockade holds promise in hepatocellular carcinoma (HCC) treatment, but its efficacy remains limited. Dysregulated polyamine metabolism and its interaction with oncogenic pathways promote tumor progression. However, the heterogeneity of polyamine metabolism and its effects on the immune microenvironment and response to immunotherapy in HCC remain unclear. Here, we aimed to investigate the prognostic and immunotherapeutic implications of polyamine metabolism in HCC. Based on polyamine-related genes, HCC patients were categorized into two clusters with distinct survival outcomes. We developed a polyamine-related signature, termed PAscore, which was found to be a strong predictor of both poor prognosis and reduced immunocyte infiltration. Notably, a high PAscore was also associated with decreased sensitivity to immunotherapy. Within the HCC microenvironment, malignant cells exhibited polyamine metabolic heterogeneity, those with high polyamine metabolic activity showed altered hallmark pathway signatures and increased communication with myeloid cells. In vitro experiments suggested that FIRRE, the gene with the greatest impact on the PAscore, significantly contributed to HCC proliferation and metastasis. This study underscores the potential of our polyamine-related signature in predicting the prognosis and immunotherapy response in HCC patients, and also reveals the polyamine metabolic heterogeneity among HCC cells that influences their crosstalk with infiltrating myeloid cells. |
| format | Article |
| id | doaj-art-42d78d1112cb4aac9fdc3fded43f32e7 |
| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj-art-42d78d1112cb4aac9fdc3fded43f32e72025-02-06T07:09:36ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-02-011610.3389/fimmu.2025.15163321516332Heterogeneity in polyamine metabolism dictates prognosis and immune checkpoint blockade response in hepatocellular carcinomaJianyan Pan0Zhong Lin1Qinchun Pan2Tao Zhu3Department of Birth Health and Genetics, The Reproductive Hospital of Guangxi Zhuang Autonomous Region, Nanning, ChinaDepartment of Birth Health and Genetics, The Reproductive Hospital of Guangxi Zhuang Autonomous Region, Nanning, ChinaSchool of Medicine & Health, Guangxi Vocational & Technical Institute of Industry, Nanning, ChinaDepartment of Pharmacy, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, ChinaImmune checkpoint blockade holds promise in hepatocellular carcinoma (HCC) treatment, but its efficacy remains limited. Dysregulated polyamine metabolism and its interaction with oncogenic pathways promote tumor progression. However, the heterogeneity of polyamine metabolism and its effects on the immune microenvironment and response to immunotherapy in HCC remain unclear. Here, we aimed to investigate the prognostic and immunotherapeutic implications of polyamine metabolism in HCC. Based on polyamine-related genes, HCC patients were categorized into two clusters with distinct survival outcomes. We developed a polyamine-related signature, termed PAscore, which was found to be a strong predictor of both poor prognosis and reduced immunocyte infiltration. Notably, a high PAscore was also associated with decreased sensitivity to immunotherapy. Within the HCC microenvironment, malignant cells exhibited polyamine metabolic heterogeneity, those with high polyamine metabolic activity showed altered hallmark pathway signatures and increased communication with myeloid cells. In vitro experiments suggested that FIRRE, the gene with the greatest impact on the PAscore, significantly contributed to HCC proliferation and metastasis. This study underscores the potential of our polyamine-related signature in predicting the prognosis and immunotherapy response in HCC patients, and also reveals the polyamine metabolic heterogeneity among HCC cells that influences their crosstalk with infiltrating myeloid cells.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1516332/fullhepatocellular carcinomapolyaminemetabolic heterogeneityimmunotherapyprognosis |
| spellingShingle | Jianyan Pan Zhong Lin Qinchun Pan Tao Zhu Heterogeneity in polyamine metabolism dictates prognosis and immune checkpoint blockade response in hepatocellular carcinoma Frontiers in Immunology hepatocellular carcinoma polyamine metabolic heterogeneity immunotherapy prognosis |
| title | Heterogeneity in polyamine metabolism dictates prognosis and immune checkpoint blockade response in hepatocellular carcinoma |
| title_full | Heterogeneity in polyamine metabolism dictates prognosis and immune checkpoint blockade response in hepatocellular carcinoma |
| title_fullStr | Heterogeneity in polyamine metabolism dictates prognosis and immune checkpoint blockade response in hepatocellular carcinoma |
| title_full_unstemmed | Heterogeneity in polyamine metabolism dictates prognosis and immune checkpoint blockade response in hepatocellular carcinoma |
| title_short | Heterogeneity in polyamine metabolism dictates prognosis and immune checkpoint blockade response in hepatocellular carcinoma |
| title_sort | heterogeneity in polyamine metabolism dictates prognosis and immune checkpoint blockade response in hepatocellular carcinoma |
| topic | hepatocellular carcinoma polyamine metabolic heterogeneity immunotherapy prognosis |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1516332/full |
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