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Systematic analysis of MCM3 in pediatric medulloblastoma via multi-omics analysis
Zhuangzhuang Liang1, Jian Yang1, Jiajia Wang1
1Department of Pediatric Neurosurgery, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Abstract:
Minichromosome maintenance proteins are DNA-dependent ATPases that bind to replication origins and allow a single round of DNA replication. One member of this family, MCM3, is reportedly active in most cancers. To systematically elucidate the mechanisms affected by aberrant MCM3 expression and evaluate its clinical significance, we analyzed multi-omics data from the GEO database and validated them in cell lines and tumor samples. First, we showed the upregulation of MCM3 in medulloblastoma (MB) at bulk and single-cell RNA sequence levels and revealed the potential role of MCM3 via DNA replication. Then we found the dysregulation of MCM3 might result from abnormal methylation of MCM3. Moreover, we discovered that MCM3 might affect varied biological processes such as apoptosis, autophagy, and ferroptosis and that MCM3 was correlated with immune components such as fibroblast and neutrophils, which were associated with overall survival in different medulloblastoma subtypes. Furthermore, we found that MCM3 expression was correlated with the IC50 values of cisplatin and etoposide. The nomogram of MCM3-related genes showed the reliable and better prediction of 1- and 5-year survival compared to current histological and molecular classifications. Overall, the results of our study demonstrated that MCM3 might serve as a potential biomarker with clinical significance and better guidance than current histological and molecular classifications for clinical decision-making.
Insights
Minichromosome maintenance protein 3 (MCM3) is upregulated in medulloblastoma, potentially impacting DNA replication and patient survival. MCM3 may serve as a novel biomarker for improved clinical decision-making.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Minichromosome maintenance (MCM) proteins are crucial for DNA replication.
- Aberrant MCM3 expression is observed in various cancers.
- Medulloblastoma (MB) is a common pediatric brain tumor with diverse subtypes.
Purpose of the Study:
- To investigate the role and clinical significance of MCM3 in medulloblastoma.
- To elucidate the mechanisms underlying MCM3 dysregulation.
- To evaluate MCM3 as a potential biomarker for MB prognosis and treatment.
Main Methods:
- Analysis of multi-omics data from the GEO database.
- Validation in cell lines and tumor samples.
- Bulk and single-cell RNA sequencing.
Main Results:
- MCM3 is upregulated in medulloblastoma at both bulk and single-cell levels, potentially via abnormal methylation.
- MCM3 expression correlates with DNA replication, apoptosis, autophagy, and ferroptosis.
- MCM3 is associated with immune cell infiltration (fibroblasts, neutrophils) and patient survival across MB subtypes.
- MCM3 expression correlates with drug sensitivity (cisplatin, etoposide) and predicts survival outcomes.
Conclusions:
- MCM3 is a potential biomarker in medulloblastoma, offering prognostic value.
- MCM3 may guide clinical decision-making, potentially outperforming current classifications.
- Further research into MCM3's role in DNA replication and cellular processes is warranted.
