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Questioning How to Define the "Ultra-High-Risk" Subgroup of Neuroblastoma Patients
A B Demir1,2, S Aktas1, Z Altun1
1Department of Basic Oncology, Institute of Oncology, Dokuz Eylul University, Izmir, Turkey.
Folia Biologica
|July 17, 2021
Summary
Anaplastic Lymphoma Kinase (ALK) gene expression may identify an ultra-high-risk subgroup in high-risk neuroblastoma patients. This finding could lead to better risk stratification and targeted therapies for this aggressive childhood cancer.
Area of Science:
- Pediatric Oncology
- Molecular Biology
- Cancer Genomics
Background:
- Neuroblastic tumors, including neuroblastoma, display significant heterogeneity impacting treatment outcomes.
- Neuroblastoma is stratified into low, intermediate, and high-risk groups, with potential for further sub-classification using novel biomarkers.
Purpose of the Study:
- To identify novel biomarkers for an ultra-high-risk subgroup within the high-risk neuroblastoma category.
- To evaluate the expression of specific genes (ALK, ATRX, HIF1a, HIF2a, H2AFX, ETV5) as potential indicators of aggressive disease.
Main Methods:
- Retrospective analysis of gene expression (RNA level) and protein expression (Immunohistochemistry for ALK) in low-risk and high-risk neuroblastoma patient cohorts.
- Statistical analyses including Spearman correlation, Mann-Whitney-U test, and ROC curve analysis were employed.
- Patient risk stratification followed the International Neuroblastoma Risk Group (INRG) Stratification System.
Main Results:
- All investigated genes, except ETV5, showed higher expression in the high-risk group compared to the low-risk group.
- Anaplastic Lymphoma Kinase (ALK) demonstrated significantly higher mRNA expression in the ultra-high-risk subgroup compared to the high-risk subgroup.
Conclusions:
- Elevated ALK mRNA expression is a potential biomarker for distinguishing the ultra-high-risk subgroup within high-risk, non-familial neuroblastoma.
- This finding may aid in refining risk stratification and guiding therapeutic strategies for patients with the most aggressive forms of neuroblastoma.
