Identification of a Five-Gene Signature Derived From MYCN Amplification and Establishment of a Nomogram for Predicting the Prognosis of Neuroblastoma

Abstract

Background: Neuroblastoma (NB), the most common solid tumor in children, exhibits vastly different genomic abnormalities and clinical behaviors. While significant progress has been made on the research of relations between clinical manifestations and genetic abnormalities, it remains a major challenge to predict the prognosis of patients to facilitate personalized treatments.Materials and Methods: Six data sets of gene expression and related clinical data were downloaded from the Gene Expression Omnibus (GEO) database, ArrayExpress database, and Therapeutically Applicable Research to Generate Effective Treatments (TARGET) database. According to the presence or absence of MYCN amplification, patients were divided into two groups. Differentially expressed genes (DEGs) were identified between the two groups. Enrichment analyses of these DEGs were performed to dig further into the molecular mechanism of NB. Stepwise Cox regression analyses were used to establish a five-gene prognostic signature whose predictive performance was further evaluated by external validation. Multivariate Cox regression analyses were used to explore independent prognostic factors for NB. The relevance of immunity was evaluated by using algorithms, and a nomogram was constructed.Results: A five-gene signature comprising CPLX3, GDPD5, SPAG6, NXPH1, and AHI1 was established. The five-gene signature had good performance in predicting survival and was demonstrated to be superior to International Neuroblastoma Staging System (INSS) staging and the MYCN amplification status. Finally, a nomogram based on the five-gene signature was established, and its clinical efficacy was demonstrated.Conclusion: Collectively, our study developed a novel five-gene signature and successfully built a prognostic nomogram that accurately predicted survival in NB. The findings presented here could help to stratify patients into subgroups and determine the optimal individualized therapy.

Plasma cell‐free DNA methylome profiling in pre‐ and post‐surgery oral cavity squamous cell carcinoma

“…However, a negative correlation was noted in patients with pancreatic cancer with regard to lymph node metastasis 59 . NXPH1 methylation has also been implicated in neuroblastoma 60 and was incorporated in a 5 gene prognostic signature where it was down regulated suggestive of playing a tumor suppressive role 61 . TBXT expression has been reported in a number of solid malignancies including head and neck, 62 lung, 63 breast, 64 colon, 64 prostate 65 and chordoma 66 —with hypothesis that it promotes epithelial‐mesenchymal transition and targeting it may help in cancer control 67 .…”

“…59 NXPH1 methylation has also been implicated in neuroblastoma 60 and was incorporated in a 5 gene prognostic signature where it was down regulated suggestive of playing a tumor suppressive role. 61 TBXT expression has been reported in a number of solid malignancies including head and neck, 62 lung, 63 breast, 64 colon, 64 prostate 65 and chordoma 66 -with hypothesis that it promotes epithelial-mesenchymal transition and targeting it may help in cancer control. 67 Promoter methylation of CDO1 has also been previously identified as diagnostic biomarkers in lung cancer.…”

Plasma cell-free DNA methylome profiling in pre- and post-surgery oral cavity squamous cell carcinoma

“…62 NXPH1 methylation has also been implicated in neuroblastoma 63 and was incorporated in a 5 gene prognostic signature where it was down regulated suggestive of playing a tumor suppressive role. 64 This suggests that tissue specific changes maybe at play. T-box transcription factor T (TBXT) expression is implicated in mesodermal specification during vertebrate development 65 and is epigenetically silenced in human fetus development at 12 weeks.…”

Integrating Bulk-seq and Single-cell-seq Reveals Estrogen and MAPK Pathways Associating with Neuroblastoma Outcome

“…7 Xia grouped patients based on MYCN status and constructed a five-gene prognostic model including CPLX3, GDPD5, SPAG6, NXPH1, and AHI1 using stepwise Cox regression, which exhibited good predictive ability in neuroblastoma prognosis. 8 Garcia constructed a neuroblastoma prognostic model using PCR, which included three genes: CHD5, PAFAH1B1, and NME1. 9 Among them, the CHD5 gene, located at 1p36 and used as a detection target for 1p deletion, has been widely applied in the prognosis stratification of neuroblastoma patients.…”