Exploratory Profiling of ABC-Family Genes Identifies a Candidate Score in Pediatric Neuroblastoma
4 affiliations
- 1Graduate School of Pharmaceutical Sciences, Chiba University, Chiba, Japan
- 2Division of Pharmacy, Chiba University Hospital, Chiba, Japan
- 3Department of Medicinal and Life Sciences, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Tokyo, Japan
- 4Research Division of Medical Data Science, Research Institute for Science and Technology, Tokyo University of Science, Chiba, Japan
Abstract
Background/Aim: High-risk pediatric neuroblastoma is characterized by frequent relapse and treatment resistance that are not fully explained by current risk stratification factors, including MYCN amplification. ATP-binding cassette (ABC) transporters are key mediators of multidrug resistance, but their clinical significance in pediatric neuroblastoma remains unclear.
Materials and Methods: Expression of all 49 human ABC-family genes were systematically analyzed using the TARGET dataset. Associations with disease stage, MYCN amplification, and overall survival were evaluated using Kaplan–Meier analysis and multivariable Cox proportional hazards models adjusted for age and MYCN amplification. Key findings were further examined in an additional dataset (Versteeg-88), from which an exploratory ABC-family gene expression-based candidate score was derived, informed by both datasets.
Results: Multiple ABC-family genes showed expression differences between stage 1 and stage 4 tumors and showed higher expression in MYCN-amplified tumors. In the multivariable Cox analysis, nine ABC-family genes showed nominal associations with overall survival after adjustment for age and MYCN amplification, although none remained significant after FDR correction. Exploratory evaluation in the Versteeg-88 dataset revealed concordant prognostic trends for genes meeting both exploratory criteria, from which an exploratory five-gene candidate score was derived. In exploratory analyses, the candidate score was associated with overall survival after adjustment for age and MYCN amplification, and this association was also observed in MYCN-non-amplified patients.
Conclusion: We provide the first comprehensive landscape of ABC-family genes dysregulation in pediatric neuroblastoma. Our findings reveal a candidate score that was associated with overall survival after adjustment for MYCN amplification, thereby suggesting prognostic heterogeneity not explained by MYCN status alone. These findings offer an initial framework for understanding coordinated ABC-family gene expression and may inform future investigations of risk-refining approaches in pediatric neuroblastoma.
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BibTeX
@article{motomura2026exploratory,
title = {{Exploratory Profiling of ABC-Family Genes Identifies a Candidate Score in Pediatric Neuroblastoma}},
author = {HITOMI MOTOMURA and KAZUNORI AKIMOTO and SHINGO YAMAZAKI},
journal = {Cancer Genomics \& Proteomics},
year = {2026},
month = oct,
doi = {10.21873/cgp.20623},
url = {https://doi.org/10.21873/cgp.20623},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Exploratory Profiling of ABC-Family Genes Identifies a Candidate Score in Pediatric Neuroblastoma
AU - HITOMI MOTOMURA
AU - KAZUNORI AKIMOTO
AU - SHINGO YAMAZAKI
PY - 2026
DA - 2026/10/31
JO - Cancer Genomics & Proteomics
DO - 10.21873/cgp.20623
UR - https://doi.org/10.21873/cgp.20623
AB - Background/Aim: High-risk pediatric neuroblastoma is characterized by frequent relapse and treatment resistance that are not fully explained by current risk stratification factors, including MYCN amplification. ATP-binding cassette (ABC) transporters are key mediators of multidrug resistance, but their clinical significance in pediatric neuroblastoma remains unclear. Materials and Methods: Expression of all 49 human ABC-family genes were systematically analyzed using the TARGET dataset. Associations with disease stage, MYCN amplification, and overall survival were evaluated using Kaplan–Meier analysis and multivariable Cox proportional hazards models adjusted for age and MYCN amplification. Key findings were further examined in an additional dataset (Versteeg-88), from which an exploratory ABC-family gene expression-based candidate score was derived, informed by both datasets. Results: Multiple ABC-family genes showed expression differences between stage 1 and stage 4 tumors and showed higher expression in MYCN-amplified tumors. In the multivariable Cox analysis, nine ABC-family genes showed nominal associations with overall survival after adjustment for age and MYCN amplification, although none remained significant after FDR correction. Exploratory evaluation in the Versteeg-88 dataset revealed concordant prognostic trends for genes meeting both exploratory criteria, from which an exploratory five-gene candidate score was derived. In exploratory analyses, the candidate score was associated with overall survival after adjustment for age and MYCN amplification, and this association was also observed in MYCN-non-amplified patients. Conclusion: We provide the first comprehensive landscape of ABC-family genes dysregulation in pediatric neuroblastoma. Our findings reveal a candidate score that was associated with overall survival after adjustment for MYCN amplification, thereby suggesting prognostic heterogeneity not explained by MYCN status alone. These findings offer an initial framework for understanding coordinated ABC-family gene expression and may inform future investigations of risk-refining approaches in pediatric neuroblastoma.
SN - 1109-6535
SN - 1790-6245
ER -