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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Main Authors: Xingning Mao, Rirong Yang, Yunkun Yan, Yanyu Zeng, Mengying Bao, Rong Huang, Yan Dai, Qingyun Zhang, Yu Ye, Jiwen Cheng, Zengnan Mo, Haiying Zhang
Format: Article
Language:English
Published: Associação Brasileira de Divulgação Científica 2025-05-01
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.
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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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