Single-cell analysis reveals potential therapeutic markers of peripheral blood mononuclear cells from bladder cancer patients
Bladder cancer is the most prevalent malignancy of the urinary tract, with significant advancements in treatment achieved over recent decades. Nonetheless, the immunological mechanisms underlying bladder cancer progression remain elusive, and only a limited number of patients derive benefit from cur...
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| Format: | Article |
| Language: | English |
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Associação Brasileira de Divulgação Científica
2025-05-01
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| Series: | Brazilian Journal of Medical and Biological Research |
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| Online Access: | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2025000100639&lng=en&tlng=en |
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| author | Xingning Mao Rirong Yang Yunkun Yan Yanyu Zeng Mengying Bao Rong Huang Yan Dai Qingyun Zhang Yu Ye Jiwen Cheng Zengnan Mo Haiying Zhang |
| author_facet | Xingning Mao Rirong Yang Yunkun Yan Yanyu Zeng Mengying Bao Rong Huang Yan Dai Qingyun Zhang Yu Ye Jiwen Cheng Zengnan Mo Haiying Zhang |
| author_sort | Xingning Mao |
| collection | DOAJ |
| description | Bladder cancer is the most prevalent malignancy of the urinary tract, with significant advancements in treatment achieved over recent decades. Nonetheless, the immunological mechanisms underlying bladder cancer progression remain elusive, and only a limited number of patients derive benefit from current immune checkpoint inhibitors. Here, we conducted a single-cell RNA sequencing analysis of 44,022 cells from peripheral blood mononuclear cell samples of bladder cancer patients and a healthy donor. Our findings indicated that the proportions of T cells and neutrophils are higher in bladder cancer patients than in the healthy donor. LAG3, HAVCR2, and CTLA4 had elevated expression levels in CD8-T2-GZMK cell clusters from patients. CD8-T7-STMN1 cells highly expressed ITGAE, CD38, and STMN1. Furthermore, NK3-CMC1, more prevalent in patients, showed a high expression of TIGIT. Additionally, Bcell2-TCL1A and Bcell3-MS4A1 were characterized by the high expression of inhibitory receptor marker genes. Gene set variation analysis suggested that Mono4-THBS1 may play a role in promoting tumor hypoxia and angiogenesis. Neu-FCGR3B exhibited high levels of IL4R and CD274 expression. Our study indicated that LAG-3 and TIM-3 may serve as novel potential immune checkpoint inhibitors in bladder cancer treatment. The phenotypes of NK3-CMC1, Bcell2-TCL1A, and Bcell3-MS4A1 might be altered by tumor progression. Mono4-THBS1 could potentially be a source of tumor-enriched monocyte-like cells. Neu-FCGR3B may play a detrimental role in the anti-tumor response and could emerge as a predictive marker for bladder cancer. Overall, these high-resolution transcriptomic data offer invaluable insights for identifying new therapeutic targets and biomarkers in bladder cancer immunotherapy. |
| format | Article |
| id | doaj-art-30eade09cb9141a5a14fe49d7edd1a1d |
| institution | Kabale University |
| issn | 1414-431X |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Associação Brasileira de Divulgação Científica |
| record_format | Article |
| series | Brazilian Journal of Medical and Biological Research |
| spelling | doaj-art-30eade09cb9141a5a14fe49d7edd1a1d2025-08-20T03:47:24ZengAssociação Brasileira de Divulgação CientíficaBrazilian Journal of Medical and Biological Research1414-431X2025-05-015810.1590/1414-431x2025e14002Single-cell analysis reveals potential therapeutic markers of peripheral blood mononuclear cells from bladder cancer patientsXingning Maohttps://orcid.org/0000-0002-9250-5342Rirong Yanghttps://orcid.org/0000-0003-1571-5925Yunkun Yanhttps://orcid.org/0000-0001-9265-4623Yanyu Zenghttps://orcid.org/0000-0001-9523-9935Mengying Baohttps://orcid.org/0000-0003-0258-1059Rong Huanghttps://orcid.org/0000-0003-2350-5557Yan Daihttps://orcid.org/0000-0001-7650-5281Qingyun Zhanghttps://orcid.org/0000-0002-7269-7009Yu Yehttps://orcid.org/0009-0009-5564-1589Jiwen Chenghttps://orcid.org/0000-0002-0599-1099Zengnan Mohttps://orcid.org/0000-0002-3047-3138Haiying Zhanghttps://orcid.org/0000-0002-3823-7498Bladder cancer is the most prevalent malignancy of the urinary tract, with significant advancements in treatment achieved over recent decades. Nonetheless, the immunological mechanisms underlying bladder cancer progression remain elusive, and only a limited number of patients derive benefit from current immune checkpoint inhibitors. Here, we conducted a single-cell RNA sequencing analysis of 44,022 cells from peripheral blood mononuclear cell samples of bladder cancer patients and a healthy donor. Our findings indicated that the proportions of T cells and neutrophils are higher in bladder cancer patients than in the healthy donor. LAG3, HAVCR2, and CTLA4 had elevated expression levels in CD8-T2-GZMK cell clusters from patients. CD8-T7-STMN1 cells highly expressed ITGAE, CD38, and STMN1. Furthermore, NK3-CMC1, more prevalent in patients, showed a high expression of TIGIT. Additionally, Bcell2-TCL1A and Bcell3-MS4A1 were characterized by the high expression of inhibitory receptor marker genes. Gene set variation analysis suggested that Mono4-THBS1 may play a role in promoting tumor hypoxia and angiogenesis. Neu-FCGR3B exhibited high levels of IL4R and CD274 expression. Our study indicated that LAG-3 and TIM-3 may serve as novel potential immune checkpoint inhibitors in bladder cancer treatment. The phenotypes of NK3-CMC1, Bcell2-TCL1A, and Bcell3-MS4A1 might be altered by tumor progression. Mono4-THBS1 could potentially be a source of tumor-enriched monocyte-like cells. Neu-FCGR3B may play a detrimental role in the anti-tumor response and could emerge as a predictive marker for bladder cancer. Overall, these high-resolution transcriptomic data offer invaluable insights for identifying new therapeutic targets and biomarkers in bladder cancer immunotherapy.http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2025000100639&lng=en&tlng=enBladder cancerPeripheral blood mononuclear cellsImmunotherapy targetsSingle-cell RNA sequencing analysisImmune subtype |
| spellingShingle | Xingning Mao Rirong Yang Yunkun Yan Yanyu Zeng Mengying Bao Rong Huang Yan Dai Qingyun Zhang Yu Ye Jiwen Cheng Zengnan Mo Haiying Zhang Single-cell analysis reveals potential therapeutic markers of peripheral blood mononuclear cells from bladder cancer patients Brazilian Journal of Medical and Biological Research Bladder cancer Peripheral blood mononuclear cells Immunotherapy targets Single-cell RNA sequencing analysis Immune subtype |
| title | Single-cell analysis reveals potential therapeutic markers of peripheral blood mononuclear cells from bladder cancer patients |
| title_full | Single-cell analysis reveals potential therapeutic markers of peripheral blood mononuclear cells from bladder cancer patients |
| title_fullStr | Single-cell analysis reveals potential therapeutic markers of peripheral blood mononuclear cells from bladder cancer patients |
| title_full_unstemmed | Single-cell analysis reveals potential therapeutic markers of peripheral blood mononuclear cells from bladder cancer patients |
| title_short | Single-cell analysis reveals potential therapeutic markers of peripheral blood mononuclear cells from bladder cancer patients |
| title_sort | single cell analysis reveals potential therapeutic markers of peripheral blood mononuclear cells from bladder cancer patients |
| topic | Bladder cancer Peripheral blood mononuclear cells Immunotherapy targets Single-cell RNA sequencing analysis Immune subtype |
| url | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2025000100639&lng=en&tlng=en |
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