Systematic analysis of MCM3 in pediatric medulloblastoma via multi-omics analysis

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.

Clinical, Histological, and Molecular Prognostic Factors in Childhood Medulloblastoma: Where Do We Stand?

“…Recent studies have revealed the promising prognostic value of various analyses based on genomic approaches that use the cell-free DNA (cfDNA) of the cerebrospinal fluid (CSF) and the different structural variants and point mutations by multiplexed droplet digital PCR (ddPCR) [128]. Moreover, Cao et al brought out the great potential of the MCM3 marker, a minichromosome-maintenance protein, through a multi-omics approach that combines single-cell RNA sequencing and proteomics analysis [129]. Undoubtedly, scientists are trying to combine state-of-the-art molecular analyses with modern massspectrometry imaging techniques that will allow for the identification of sub-group-specific tumor-cell populations whose unique functions can be exploited for future prognostic and therapeutic strategies.…”

The MCM3-AKT/Twist Pathway: Unveiling Its Prognostic Significance in Hepatocellular Carcinoma Progression

“…In these contexts, MCM3 has been proposed as a prognostic marker, with its overexpression correlating with poor survival outcomes(H.-T. Li et al, 2020;L. Li et al, 2012;Z. Liang et al, 2022;Ma et al, 2021;Zhou et al, 2020).…”