Integration of bulk and single-cell RNA-seq reveals prognostic gene signatures in patients with bladder cancer treated with immune checkpoint inhibitors
Abstract Immune checkpoint inhibitors have significantly advanced research in oncology and are used to successfully treat patients with bladder cancer (BC). However, as the benefits of programmed death-1/ programmed death-ligand-1 blockade immunotherapy do not extend to all patients with BC, biomark...
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Springer
2024-12-01
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| Series: | Cancer Immunology, Immunotherapy |
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| Online Access: | https://doi.org/10.1007/s00262-024-03839-7 |
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| author | Mina Cho Hyun Chang Ju Han Kim |
| author_facet | Mina Cho Hyun Chang Ju Han Kim |
| author_sort | Mina Cho |
| collection | DOAJ |
| description | Abstract Immune checkpoint inhibitors have significantly advanced research in oncology and are used to successfully treat patients with bladder cancer (BC). However, as the benefits of programmed death-1/ programmed death-ligand-1 blockade immunotherapy do not extend to all patients with BC, biomarkers are required to improve prognostic stratification. This study aims to identify reliable biomarkers to enhance the prediction of treatment outcomes. Bulk RNA expression data from a BC cohort (GSE176307) receiving ICI and single-cell sequencing data from patients with BC (GSE135337) were collected. We identified differentially expressed genes (DEGs) within cells that were associated with favorable survival outcomes and developed a predictive bladder cancer gene signature (BC-GS). Subsequently, we performed pathway enrichment analysis using the Reactome database. We used two independent datasets to validate the BC-GS. Patients with low BC-GS had a significantly shorter overall survival (OS) than those with high BC-GS (p < 0.05, p < 0.001, respectively). Additionally, patients with a concurrently low BC-GS score and low tumor mutation burden (TMB) in GSE176307 and the two validation datasets exhibited an increased risk of death. Genes in the BC-GS were predominantly involved in CD8+ T cell activation, antigen presentation, and immune checkpoint pathways. CIBERSORT analysis revealed differences in CD4+ T cells and macrophages between the high and low BC-GS groups. This study demonstrated the prognostic significance of the BC-GS in patients with BC treated with ICI. The combined assessment of the BC-GS and TMB may provide a sophisticated prognostic approach to enhance patient stratification for ICI treatment in BC. |
| format | Article |
| id | doaj-art-33ab5d4c870542669b2b711cc256ab01 |
| institution | Kabale University |
| issn | 1432-0851 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Springer |
| record_format | Article |
| series | Cancer Immunology, Immunotherapy |
| spelling | doaj-art-33ab5d4c870542669b2b711cc256ab012025-02-02T12:26:41ZengSpringerCancer Immunology, Immunotherapy1432-08512024-12-0174111110.1007/s00262-024-03839-7Integration of bulk and single-cell RNA-seq reveals prognostic gene signatures in patients with bladder cancer treated with immune checkpoint inhibitorsMina Cho0Hyun Chang1Ju Han Kim2Division of Biomedical Informatics, Seoul National University Biomedical Informatics (SNUBI), Seoul National University College of MedicineMedical Oncology and Hematology, College of Medicine, International St Mary’s Hospital, Catholic Kwandong UniversityDivision of Biomedical Informatics, Seoul National University Biomedical Informatics (SNUBI), Seoul National University College of MedicineAbstract Immune checkpoint inhibitors have significantly advanced research in oncology and are used to successfully treat patients with bladder cancer (BC). However, as the benefits of programmed death-1/ programmed death-ligand-1 blockade immunotherapy do not extend to all patients with BC, biomarkers are required to improve prognostic stratification. This study aims to identify reliable biomarkers to enhance the prediction of treatment outcomes. Bulk RNA expression data from a BC cohort (GSE176307) receiving ICI and single-cell sequencing data from patients with BC (GSE135337) were collected. We identified differentially expressed genes (DEGs) within cells that were associated with favorable survival outcomes and developed a predictive bladder cancer gene signature (BC-GS). Subsequently, we performed pathway enrichment analysis using the Reactome database. We used two independent datasets to validate the BC-GS. Patients with low BC-GS had a significantly shorter overall survival (OS) than those with high BC-GS (p < 0.05, p < 0.001, respectively). Additionally, patients with a concurrently low BC-GS score and low tumor mutation burden (TMB) in GSE176307 and the two validation datasets exhibited an increased risk of death. Genes in the BC-GS were predominantly involved in CD8+ T cell activation, antigen presentation, and immune checkpoint pathways. CIBERSORT analysis revealed differences in CD4+ T cells and macrophages between the high and low BC-GS groups. This study demonstrated the prognostic significance of the BC-GS in patients with BC treated with ICI. The combined assessment of the BC-GS and TMB may provide a sophisticated prognostic approach to enhance patient stratification for ICI treatment in BC.https://doi.org/10.1007/s00262-024-03839-7Bladder cancerBladder cancer gene signatureImmune checkpoint inhibitorsTumor microenvironmentTumor mutation burden |
| spellingShingle | Mina Cho Hyun Chang Ju Han Kim Integration of bulk and single-cell RNA-seq reveals prognostic gene signatures in patients with bladder cancer treated with immune checkpoint inhibitors Cancer Immunology, Immunotherapy Bladder cancer Bladder cancer gene signature Immune checkpoint inhibitors Tumor microenvironment Tumor mutation burden |
| title | Integration of bulk and single-cell RNA-seq reveals prognostic gene signatures in patients with bladder cancer treated with immune checkpoint inhibitors |
| title_full | Integration of bulk and single-cell RNA-seq reveals prognostic gene signatures in patients with bladder cancer treated with immune checkpoint inhibitors |
| title_fullStr | Integration of bulk and single-cell RNA-seq reveals prognostic gene signatures in patients with bladder cancer treated with immune checkpoint inhibitors |
| title_full_unstemmed | Integration of bulk and single-cell RNA-seq reveals prognostic gene signatures in patients with bladder cancer treated with immune checkpoint inhibitors |
| title_short | Integration of bulk and single-cell RNA-seq reveals prognostic gene signatures in patients with bladder cancer treated with immune checkpoint inhibitors |
| title_sort | integration of bulk and single cell rna seq reveals prognostic gene signatures in patients with bladder cancer treated with immune checkpoint inhibitors |
| topic | Bladder cancer Bladder cancer gene signature Immune checkpoint inhibitors Tumor microenvironment Tumor mutation burden |
| url | https://doi.org/10.1007/s00262-024-03839-7 |
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