Integrated bioinformatics and functional studies identify CDK9 as a potential prognostic biomarker and therapeutic target in AML
Abstract Background Acute myeloid leukemia (AML) is a highly heterogeneous disease characterized by complex genetic and molecular features that contribute to poor prognosis and low cure rates. Therefore, identifying novel therapeutic targets is crucial for improving treatment efficacy and patient su...
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| Format: | Article |
| Language: | English |
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Springer
2025-06-01
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| Series: | Discover Oncology |
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| Online Access: | https://doi.org/10.1007/s12672-025-02841-4 |
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| author | Zhibin Xie Yang Xia Zhongyu Li Mengmeng Zhang Yuanyuan Tan Yuqing Han Meng Wang Pingping Zhang Jiajia Li |
| author_facet | Zhibin Xie Yang Xia Zhongyu Li Mengmeng Zhang Yuanyuan Tan Yuqing Han Meng Wang Pingping Zhang Jiajia Li |
| author_sort | Zhibin Xie |
| collection | DOAJ |
| description | Abstract Background Acute myeloid leukemia (AML) is a highly heterogeneous disease characterized by complex genetic and molecular features that contribute to poor prognosis and low cure rates. Therefore, identifying novel therapeutic targets is crucial for improving treatment efficacy and patient survival. This study investigated the potential role of cyclin-dependent kinase 9 (CDK9), a known regulator of gene expression, in AML pathogenesis and prognosis. Methods This study employed multiple bioinformatics approaches, including analysis of CDK9 expression across various cancers using the Tumor Immune Estimation Resource (TIMER2.0) database and further investigation of its expression and prognostic significance in AML using data from the Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases. Survival analysis and Cox regression analysis were used to assess the association between CDK9 expression and patient prognosis. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) were performed to elucidate the pathways and biological processes influenced by CDK9. Furthermore, the relationship between CDK9 expression and tumor immune infiltration was evaluated, and a protein–protein interaction (PPI) network was constructed. In vitro experiments, including Western blotting, CCK-8 assays, and flow cytometry, were conducted to validate the bioinformatics findings. Results Bioinformatics analysis revealed significantly elevated CDK9 expression in AML samples, which correlated with poor patient prognosis. Functional enrichment analysis indicated that CDK9 is involved in key pathways related to cell proliferation, differentiation, and the tumor microenvironment. Moreover, the study observed a strong correlation between CDK9 expression and altered immune cell infiltration, suggesting a potential role in immune evasion. In vitro experiments confirmed that CDK9 overexpression promoted AML cell proliferation and inhibited apoptosis. Additionally, CDK9 showed a strong correlation with epithelial-mesenchymal transition (EMT)-related proteins, suggesting a potential role in AML progression and the EMT process. Conclusions This study demonstrates that CDK9 is a potential prognostic biomarker and therapeutic target in AML. Its involvement in multiple key pathways during AML development and its influence on the tumor immune microenvironment support further exploration of CDK9-targeted therapies to improve AML treatment outcomes. |
| format | Article |
| id | doaj-art-0217a3ea7ac04ac6bfbcbf85860c2b0c |
| institution | Kabale University |
| issn | 2730-6011 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Springer |
| record_format | Article |
| series | Discover Oncology |
| spelling | doaj-art-0217a3ea7ac04ac6bfbcbf85860c2b0c2025-08-20T03:45:31ZengSpringerDiscover Oncology2730-60112025-06-0116111410.1007/s12672-025-02841-4Integrated bioinformatics and functional studies identify CDK9 as a potential prognostic biomarker and therapeutic target in AMLZhibin Xie0Yang Xia1Zhongyu Li2Mengmeng Zhang3Yuanyuan Tan4Yuqing Han5Meng Wang6Pingping Zhang7Jiajia Li8Department of Hematology, First Affiliated Hospital of Bengbu Medical UniversityDepartment of Finance, First Affiliated Hospital of Bengbu Medical UniversityDepartment of Hematology, The Third People’s Hospital of BengbuDepartment of Hematology, First Affiliated Hospital of Bengbu Medical UniversityDepartment of Hematology, First Affiliated Hospital of Bengbu Medical UniversityBengbu Medical UniversityDepartment of Hematology, First Affiliated Hospital of Bengbu Medical UniversityDepartment of Hematology, First Affiliated Hospital of Bengbu Medical UniversityDepartment of Hematology, First Affiliated Hospital of Bengbu Medical UniversityAbstract Background Acute myeloid leukemia (AML) is a highly heterogeneous disease characterized by complex genetic and molecular features that contribute to poor prognosis and low cure rates. Therefore, identifying novel therapeutic targets is crucial for improving treatment efficacy and patient survival. This study investigated the potential role of cyclin-dependent kinase 9 (CDK9), a known regulator of gene expression, in AML pathogenesis and prognosis. Methods This study employed multiple bioinformatics approaches, including analysis of CDK9 expression across various cancers using the Tumor Immune Estimation Resource (TIMER2.0) database and further investigation of its expression and prognostic significance in AML using data from the Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases. Survival analysis and Cox regression analysis were used to assess the association between CDK9 expression and patient prognosis. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) were performed to elucidate the pathways and biological processes influenced by CDK9. Furthermore, the relationship between CDK9 expression and tumor immune infiltration was evaluated, and a protein–protein interaction (PPI) network was constructed. In vitro experiments, including Western blotting, CCK-8 assays, and flow cytometry, were conducted to validate the bioinformatics findings. Results Bioinformatics analysis revealed significantly elevated CDK9 expression in AML samples, which correlated with poor patient prognosis. Functional enrichment analysis indicated that CDK9 is involved in key pathways related to cell proliferation, differentiation, and the tumor microenvironment. Moreover, the study observed a strong correlation between CDK9 expression and altered immune cell infiltration, suggesting a potential role in immune evasion. In vitro experiments confirmed that CDK9 overexpression promoted AML cell proliferation and inhibited apoptosis. Additionally, CDK9 showed a strong correlation with epithelial-mesenchymal transition (EMT)-related proteins, suggesting a potential role in AML progression and the EMT process. Conclusions This study demonstrates that CDK9 is a potential prognostic biomarker and therapeutic target in AML. Its involvement in multiple key pathways during AML development and its influence on the tumor immune microenvironment support further exploration of CDK9-targeted therapies to improve AML treatment outcomes.https://doi.org/10.1007/s12672-025-02841-4CDK9Acute myeloid leukemiaBiomarkersImmune infiltrationPrognosis |
| spellingShingle | Zhibin Xie Yang Xia Zhongyu Li Mengmeng Zhang Yuanyuan Tan Yuqing Han Meng Wang Pingping Zhang Jiajia Li Integrated bioinformatics and functional studies identify CDK9 as a potential prognostic biomarker and therapeutic target in AML Discover Oncology CDK9 Acute myeloid leukemia Biomarkers Immune infiltration Prognosis |
| title | Integrated bioinformatics and functional studies identify CDK9 as a potential prognostic biomarker and therapeutic target in AML |
| title_full | Integrated bioinformatics and functional studies identify CDK9 as a potential prognostic biomarker and therapeutic target in AML |
| title_fullStr | Integrated bioinformatics and functional studies identify CDK9 as a potential prognostic biomarker and therapeutic target in AML |
| title_full_unstemmed | Integrated bioinformatics and functional studies identify CDK9 as a potential prognostic biomarker and therapeutic target in AML |
| title_short | Integrated bioinformatics and functional studies identify CDK9 as a potential prognostic biomarker and therapeutic target in AML |
| title_sort | integrated bioinformatics and functional studies identify cdk9 as a potential prognostic biomarker and therapeutic target in aml |
| topic | CDK9 Acute myeloid leukemia Biomarkers Immune infiltration Prognosis |
| url | https://doi.org/10.1007/s12672-025-02841-4 |
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