Construction of the bromodomain-containing protein-associated prognostic model in triple-negative breast cancer
Abstract Background Bromodomain-containing protein (BRD) play a pivotal role in the development and progression of malignant tumours. This study aims to identify prognostic genes linked to BRD-related genes (BRDRGs) in patients with triple-negative breast cancer (TNBC) and to construct a novel progn...
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BMC
2025-01-01
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| Series: | Cancer Cell International |
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| Online Access: | https://doi.org/10.1186/s12935-025-03648-7 |
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| author | Wei Chen Yushuai Yu Chenxi Wang Zirong Jiang Xiewei Huang Yidan Lin Hongjing Han Qing Wang Hui Zhang |
| author_facet | Wei Chen Yushuai Yu Chenxi Wang Zirong Jiang Xiewei Huang Yidan Lin Hongjing Han Qing Wang Hui Zhang |
| author_sort | Wei Chen |
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| description | Abstract Background Bromodomain-containing protein (BRD) play a pivotal role in the development and progression of malignant tumours. This study aims to identify prognostic genes linked to BRD-related genes (BRDRGs) in patients with triple-negative breast cancer (TNBC) and to construct a novel prognostic model. Methods Data from TCGA-TNBC, GSE135565, and GSE161529 were retrieved from public databases. GSE161529 was used to identify key cell types. The BRDRGs score in TCGA-TNBC was calculated using single-sample Gene Set Enrichment Analysis (ssGSEA). Differential expression analysis was performed to identify differentially expressed genes (DEGs): DEGs1 in key cells, DEGs2 between tumours and controls and DEGs3 in high and low BRDRGs score subgroups in TCGA-TNBC. Differentially expressed BRDRGs (DE-BRDRGs) were determined by overlapping DEGs1, DEGs2 and DEGs3. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and protein-protein interaction (PPI) network analysis were conducted to investigate active pathways and molecular interactions. Prognostic genes were selected through univariate Cox regression and least absolute shrinkage and selection operator (LASSO) regression analyses to construct a risk model and calculate risk scores. TNBC samples from TCGA-TNBC were classified into high and low-risk groups based on the median risk score. Additionally, correlations with clinical characteristics, Gene Set Enrichment Analysis (GSEA), immune analysis, and pseudotime analysis were performed. Results A total of 120 DE-BRDRGs were identified by overlapping 605 DEGs1 from four key cell types, 10,776 DEGs2, and 4,497 DEGs3. GO analysis revealed enriched terms such as ‘apoptotic process,’ ‘immune response,’ and ‘regulation of the cell cycle,’ while 56 KEGG pathways, including the ‘MAPK signaling pathway,’ were associated with DE-BRDRGs. A risk model comprising six prognostic genes (KRT6A, PGF, ABCA1, EDNRB, CTSD and GJA4) was constructed. A nomogram based on independent prognostic factors was also developed. Immune cell abundance was significantly higher in high-risk group. In both risk groups, TP53 exhibited the highest mutation frequency. The expression of KRT6A, ABCA1, EDNRB, and CTSD went decreased progressively in pseudotime. Conclusion A novel prognostic model for TNBC associated with BRDRGs was developed and validated, providing fresh insights into the relationship between BRD and TNBC. |
| format | Article |
| id | doaj-art-b59ed19209fd4af9835698b4ba3fe76b |
| institution | Kabale University |
| issn | 1475-2867 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
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| series | Cancer Cell International |
| spelling | doaj-art-b59ed19209fd4af9835698b4ba3fe76b2025-01-19T12:39:34ZengBMCCancer Cell International1475-28672025-01-0125112110.1186/s12935-025-03648-7Construction of the bromodomain-containing protein-associated prognostic model in triple-negative breast cancerWei Chen0Yushuai Yu1Chenxi Wang2Zirong Jiang3Xiewei Huang4Yidan Lin5Hongjing Han6Qing Wang7Hui Zhang8Department of Breast Surgery, Fujian Provincial Hospital, Shengli Clinical Medical College of Fuiian Medical University, Fuzhou University Affiliated Provincial HospitalFujian Medical UniversityThird Department of Breast Surgery, The Third Affiliated Hospital of Kunming Medical University&Yunnan Cancer HospitalDepartment of Breast and Thyroid Surgery, Ningde Clinical Medical College of Fujian Medical University, Ningde Municipal Hospital of Ningde Normal UniversityFujian Medical UniversityFujian Medical UniversitySection 2 of General Surgery Department, The Second People’s Hospital of JingdezhenFujian Medical UniversityDepartment of Breast Surgery, Fujian Provincial Hospital, Shengli Clinical Medical College of Fuiian Medical University, Fuzhou University Affiliated Provincial HospitalAbstract Background Bromodomain-containing protein (BRD) play a pivotal role in the development and progression of malignant tumours. This study aims to identify prognostic genes linked to BRD-related genes (BRDRGs) in patients with triple-negative breast cancer (TNBC) and to construct a novel prognostic model. Methods Data from TCGA-TNBC, GSE135565, and GSE161529 were retrieved from public databases. GSE161529 was used to identify key cell types. The BRDRGs score in TCGA-TNBC was calculated using single-sample Gene Set Enrichment Analysis (ssGSEA). Differential expression analysis was performed to identify differentially expressed genes (DEGs): DEGs1 in key cells, DEGs2 between tumours and controls and DEGs3 in high and low BRDRGs score subgroups in TCGA-TNBC. Differentially expressed BRDRGs (DE-BRDRGs) were determined by overlapping DEGs1, DEGs2 and DEGs3. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and protein-protein interaction (PPI) network analysis were conducted to investigate active pathways and molecular interactions. Prognostic genes were selected through univariate Cox regression and least absolute shrinkage and selection operator (LASSO) regression analyses to construct a risk model and calculate risk scores. TNBC samples from TCGA-TNBC were classified into high and low-risk groups based on the median risk score. Additionally, correlations with clinical characteristics, Gene Set Enrichment Analysis (GSEA), immune analysis, and pseudotime analysis were performed. Results A total of 120 DE-BRDRGs were identified by overlapping 605 DEGs1 from four key cell types, 10,776 DEGs2, and 4,497 DEGs3. GO analysis revealed enriched terms such as ‘apoptotic process,’ ‘immune response,’ and ‘regulation of the cell cycle,’ while 56 KEGG pathways, including the ‘MAPK signaling pathway,’ were associated with DE-BRDRGs. A risk model comprising six prognostic genes (KRT6A, PGF, ABCA1, EDNRB, CTSD and GJA4) was constructed. A nomogram based on independent prognostic factors was also developed. Immune cell abundance was significantly higher in high-risk group. In both risk groups, TP53 exhibited the highest mutation frequency. The expression of KRT6A, ABCA1, EDNRB, and CTSD went decreased progressively in pseudotime. Conclusion A novel prognostic model for TNBC associated with BRDRGs was developed and validated, providing fresh insights into the relationship between BRD and TNBC.https://doi.org/10.1186/s12935-025-03648-7Triple-negative breast cancerBromodomain-containing proteinImmune microenvironmentPrognosis |
| spellingShingle | Wei Chen Yushuai Yu Chenxi Wang Zirong Jiang Xiewei Huang Yidan Lin Hongjing Han Qing Wang Hui Zhang Construction of the bromodomain-containing protein-associated prognostic model in triple-negative breast cancer Cancer Cell International Triple-negative breast cancer Bromodomain-containing protein Immune microenvironment Prognosis |
| title | Construction of the bromodomain-containing protein-associated prognostic model in triple-negative breast cancer |
| title_full | Construction of the bromodomain-containing protein-associated prognostic model in triple-negative breast cancer |
| title_fullStr | Construction of the bromodomain-containing protein-associated prognostic model in triple-negative breast cancer |
| title_full_unstemmed | Construction of the bromodomain-containing protein-associated prognostic model in triple-negative breast cancer |
| title_short | Construction of the bromodomain-containing protein-associated prognostic model in triple-negative breast cancer |
| title_sort | construction of the bromodomain containing protein associated prognostic model in triple negative breast cancer |
| topic | Triple-negative breast cancer Bromodomain-containing protein Immune microenvironment Prognosis |
| url | https://doi.org/10.1186/s12935-025-03648-7 |
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