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Published on: October 4, 2019
Prognostic value of microRNA-125a expression status in molecular groups of pediatric medulloblastoma
Soheir M Hamam1, Eman Abdelzaher1, Shady H Fadel2
1Pathology department, Faculty of Medicine, Alexandria University, Alexandria, Egypt.
Purpose:
Medulloblastoma (MB) is the most common malignant pediatric brain tumor. Current treatment allows decent survival rates but often with life-long morbidity. Molecular classification provides a base for novel therapeutic approaches. However, these groups are heterogeneous. MicroRNA-125a has a tumor suppressor function. It is downregulated in several tumors. The expression of microRNA-125a in MB patients remains unclear. Therefore, this study was designed to evaluate the expression of microRNA-125a in molecular groups of pediatric MB patients in Egyptian population and its clinical significance.
Methods:
Formalin-fixed, paraffin-embedded tissue blocks from 50 pediatric MB patients were retrospectively collected. Immunohistochemistry for β-catenin, GAB1, YAP1, and p53 was done for molecular classification. MicroRNA-125a expression analysis was done using qRT-PCR. Follow-up data were obtained from patients' records.
Results:
MicroRNA-125a expression was significantly lower in MB patients showing large cell/anaplastic (LC/A) histology and in the non-WNT/non-SHH group. Lower levels of microRNA-125a showed a tendency toward poor survival rates; however, difference was not significant. Infants and larger preoperative tumor size were significantly associated with lower survival rates. On a multivariate analysis, preoperative tumor size was an independent prognostic factor.
Conclusion:
MicroRNA-125a expression was significantly lower in categories of pediatric MB patients with worse prognosis namely LC/A histology and the non-WNT/non-SHH group suggesting a pathogenetic role. MicroRNA-125a expression could represent a promising prognostic factor and a potential therapeutic target in the non-WNT/non-SHH group which represents the most common and the most heterogeneous group of pediatric MBs coupled with the highest rates of disseminated disease. Preoperative tumor size represents an independent prognostic factor.
Insights
MicroRNA-125a is downregulated in pediatric medulloblastoma (MB) with poor prognostic features like large cell/anaplastic histology and the non-WNT/non-SHH molecular group. Lower microRNA-125a levels may indicate a worse prognosis and suggest therapeutic potential.
Area of Science:
- Pediatric oncology
- Molecular biology
- Genetics
Background:
- Medulloblastoma (MB) is the most common pediatric brain tumor, with current treatments causing significant long-term morbidity.
- Molecular subgroups of MB exist, but they remain heterogeneous, necessitating further investigation for targeted therapies.
- MicroRNA-125a, a known tumor suppressor, is downregulated in various cancers, but its role in MB is not well-defined.
Purpose of the Study:
- To investigate the expression levels of microRNA-125a in different molecular subgroups of pediatric medulloblastoma patients.
- To determine the clinical significance and prognostic value of microRNA-125a expression in Egyptian pediatric MB patients.
Main Methods:
- Retrospective collection of formalin-fixed, paraffin-embedded tissues from 50 pediatric MB patients.
- Immunohistochemistry for β-catenin, GAB1, YAP1, and p53 for molecular classification.
- Quantitative reverse transcription PCR (qRT-PCR) for microRNA-125a expression analysis and correlation with clinical data.
Main Results:
- MicroRNA-125a expression was significantly lower in MB patients with large cell/anaplastic (LC/A) histology and those in the non-WNT/non-SHH molecular group.
- Lower microRNA-125a levels showed a trend towards poorer survival, though not statistically significant.
- Infants and larger preoperative tumor size were significantly associated with reduced survival rates, with tumor size being an independent prognostic factor.
Conclusions:
- Reduced microRNA-125a expression correlates with unfavorable prognostic indicators (LC/A histology, non-WNT/non-SHH group) in pediatric MB, suggesting a pathogenetic role.
- MicroRNA-125a may serve as a prognostic biomarker and a potential therapeutic target, particularly in the heterogeneous non-WNT/non-SHH subgroup.
- Preoperative tumor size is a significant independent prognostic factor in pediatric medulloblastoma.
