Identification and validation of mitochondrial and programmed cell death-related prognostic markers in pediatric
Xiaoyan Hu1,2, Qiang Zhao2, Wei Deng2
1The First Clinical Medical School, Lanzhou University, Lanzhou, China.
Insights
Researchers identified three key genes (PDHA1, OGG1, OPA1) as potential prognostic markers for pediatric acute myeloid leukemia (AML). This discovery could lead to improved targeted therapies for this aggressive childhood cancer.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Pediatric acute myeloid leukemia (AML) presents a significant challenge due to poor prognosis and low survival rates after recurrence.
- The roles of mitochondria and programmed cell death (PCD) in pediatric AML are not well understood.
- Identifying prognostic genes linked to PCD and mitochondrial function is crucial for advancing therapeutic strategies.
Purpose of the Study:
- To identify novel prognostic genes associated with programmed cell death (PCD) and mitochondrial function in pediatric acute myeloid leukemia (AML).
- To develop and validate a prognostic model for pediatric AML based on identified genes.
- To explore potential therapeutic targets and immune microenvironment characteristics in pediatric AML.
Main Methods:
- Transcriptomic data analysis to identify differentially expressed genes (DEGs) intersecting with PCD-related and mitochondrial-related genes.
- Development and validation of a prognostic model and nomogram using regression analyses.
- Functional enrichment, immune cell profiling, molecular network analysis, drug sensitivity prediction, and RT-qPCR validation.
Main Results:
- Three genes—PDHA1, OGG1, and OPA1—were identified as significant prognostic markers for pediatric AML.
- The developed prognostic model and nomogram demonstrated robust predictive power in internal and external validation.
- Pathway analysis revealed involvement of DNA replication and EMT; 14 immune cell types were differentially abundant; hsa-miR-199a-5p was found to regulate PDHA1 and OGG1.
Conclusions:
- PDHA1, OGG1, and OPA1 show promise as prognostic markers for pediatric AML, offering potential for targeted therapy development.
- The findings provide valuable insights into the molecular mechanisms underlying pediatric AML.
- Further validation in larger, diverse clinical cohorts is necessary to confirm clinical applicability.
Background:
Pediatric acute myeloid leukemia (AML) is characterized by poor prognosis and low survival rates following recurrence. While mitochondria and programmed cell death (PCD) are implicated in various diseases, their role in pediatric AML remains poorly understood. Identifying prognostic genes associated with PCD and mitochondrial function could enhance therapeutic approaches.
Methods:
Transcriptomic data and gene sets were sourced from public databases. Differentially expressed genes (DEGs) that intersected with PCD-related genes (PCD-RGs) and mitochondrial-related genes (mito-RGs) were selected as candidate genes. Regression analyses were performed to identify prognostic genes, which were then used to develop and validate a prognostic model. A nomogram was constructed, followed by functional analysis, immune microenvironment assessment, molecular regulatory network investigation, drug sensitivity profiling, and clinical validation through RT-qPCR.
Results:
Twenty-six candidate genes were identified, with three-PDHA1, OGG1, and OPA1-confirmed as potential prognostic markers through regression analyses. The prognostic model demonstrated robustness in both internal and external validations, and the nomogram exhibited good predictive power. Pathway enrichment analysis highlighted the involvement of DNA replication and epithelial-mesenchymal transition, alongside 14 differentially abundant immune cells (p < 0.05). Molecular network analysis indicated that hsa-miR-199a-5p regulates PDHA1 and OGG1. Drug sensitivity profiling identified potential therapeutic agents, including SB505124_1194. RT-qPCR validation confirmed consistent expression patterns for the prognostic genes.
Conclusions:
PDHA1, OGG1, and OPA1 were identified as potential prognostic markers for pediatric AML, providing valuable insights for the development of targeted therapeutic strategies. However, further validation in larger and more diverse clinical cohorts is still required to confirm its clinical applicability.
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