Identification and External Validation of a Transcription Factor-Related Prognostic Signature in Pediatric Neuroblastoma

Abstract

Background. Neuroblastoma is a common solid tumor originating from the sympathetic nervous system, commonly found in children, and it is one of the leading causes of tumor-related deaths in children. In addition to pathological features, molecular-level features, such as how much gene expression is present and the mutational profile, may provide useful information for the precise treatment of neuroblastoma. Transcription factors (TFs) play an important regulatory role in all aspects of cellular life activities. But there are currently no studies on transcription factor-based biomarkers of neuroblastoma prognosis, and this study is much needed. Methods. We downloaded RNA transcriptome data and clinical data from the TARGET database to construct a prognostic model. The prognostic model was constructed by using univariate Cox analysis, LASSO, and multivariate Cox regression. We divided the patients into low-risk and high-risk groups using the median value of the risk score as the cut-off. Then, we validated the prognostic model with the dataset GSE49710. Results. We constructed a prognostic model consisting of eight genes (SATB1, ZNF564, SOX14, EN1, IKZF2, SLC2A4RG, FOXJ2, and ZNF521). Patients in the high-risk group had a lower survival rate than those in the low-risk group. The area under the 3-year ROC curve of the model reached 0.825, suggesting a good predictive efficacy. We performed target gene prediction for the eight transcription factors in the model using six online databases and found that TUT1 may be a target gene for transcription factor EN1 and is associated with immune infiltration. Conclusion. This prognostic model consisting of eight transcription factor-associated genes demonstrated reliable predictive efficacy. This prediction model may provide new potential targets for the treatment of neuroblastoma and personalized monitoring of neuroblastoma patients with high and low risk.