Rosswog, Carolina, Schmidt, Rene, Oberthuer, Andre, Juraeva, Dilafruz, Brors, Benedikt ORCID: 0000-0001-5940-3101, Engesser, Anne, Kahlert, Yvonne, Volland, Ruth, Bartenhagen, Christoph, Simon, Thorsten, Berthold, Frank, Hero, Barbara, Faldum, Andreas and Fischer, Matthias (2017). Molecular Classification Substitutes for the Prognostic Variables Stage, Age, and MYCN Status in Neuroblastoma Risk Assessment. Neoplasia, 19 (12). S. 982 - 991. NEW YORK: ELSEVIER SCIENCE INC. ISSN 1476-5586

Full text not available from this repository.

Abstract

BACKGROUND: Current risk stratification systems for neuroblastoma patients consider clinical, histopathological, and genetic variables, and additional prognostic markers have been proposed in recent years. We here sought to select highly informative covariates in a multistep strategy based on consecutive Cox regression models, resulting in a risk score that integrates hazard ratios of prognostic variables. METHODS: A cohort of 695 neuroblastoma patients was divided into a discovery set (n = 75) for multigene predictor generation, a training set (n = 411) for risk score development, and a validation set (n = 209). Relevant prognostic variables were identified by stepwise multivariable L1-penalized least absolute shrinkage and selection operator (LASSO) Cox regression, followed by backward selection in multivariable Cox regression, and then integrated into a novel risk score. RESULTS: The variables stage, age, MYCN status, and two multigene predictors, NB-th24 and NB-th44, were selected as independent prognostic markers by LASSO Cox regression analysis. Following backward selection, only the multigene predictors were retained in the final model. Integration of these classifiers in a risk scoring system distinguished three patient subgroups that differed substantially in their outcome. The scoring system discriminated patients with diverging outcome in the validation cohort (5-year event-free survival, 84.9 +/- 3.4 vs 63.6 +/- 14.5 vs 31.0 +/- 5.4; P < .001), and its prognostic value was validated by multivariable analysis. CONCLUSION: We here propose a translational strategy for developing risk assessment systems based on hazard ratios of relevant prognostic variables. Our final neuroblastoma risk score comprised two multigene predictors only, supporting the notion that molecular properties of the tumor cells strongly impact clinical courses of neuroblastoma patients.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Rosswog, CarolinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schmidt, ReneUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Oberthuer, AndreUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Juraeva, DilafruzUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Brors, BenediktUNSPECIFIEDorcid.org/0000-0001-5940-3101UNSPECIFIED
Engesser, AnneUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kahlert, YvonneUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Volland, RuthUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bartenhagen, ChristophUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Simon, ThorstenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Berthold, FrankUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hero, BarbaraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Faldum, AndreasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fischer, MatthiasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-209500
DOI: 10.1016/j.neo.2017.09.006
Journal or Publication Title: Neoplasia
Volume: 19
Number: 12
Page Range: S. 982 - 991
Date: 2017
Publisher: ELSEVIER SCIENCE INC
Place of Publication: NEW YORK
ISSN: 1476-5586
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
YOUNG-ADULTS; STRATIFICATION; EXPRESSION; GENE; ADOLESCENTS; ALK; REARRANGEMENTS; AMPLIFICATION; ACTIVATION; PREDICTIONMultiple languages
OncologyMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/20950

Downloads

Downloads per month over past year

Altmetric

Export

Actions (login required)

View Item View Item