Identification of MYCN-Related Gene as a Potential Biomarker for Neuroblastoma Prognostic Model by Integrated Analysis and Quantitative Real-Time PCR

DNA Cell Biol. 2021 Feb;40(2):332-347. doi: 10.1089/dna.2020.6193. Epub 2020 Dec 30.

Abstract

Neuroblastoma (NB) has the highest incidence of all extracranial solid tumors in children and is highly lethal. This study aims to establish a prognostic model of NB with MYCN-related genes. We determined the gene expression profiles of 900 NB samples from the UCSC database and four Gene Expression Omnibus (GEO) data sets, and performed a comprehensive bioinformatics analysis and clinical sample verification. After univariate Cox regression, least absolute shrinkage and selection operator (Lasso), and multivariate Cox regression analyses, four (AKR1C1, CHD5, PDE4DIP, and PRKACB) genes were finally selected and used to construct a risk score prognostic model. In the UCSC data set, the high-risk group exhibited a significantly worse prognosis than the low-risk group. In addition, the nomogram, which includes prognostic markers and clinical factors, demonstrates high prognostic value. Finally, the differential expression of the four genes in the model was verified by quantitative real-time PCR in clinical tissues. These findings of MYCN-related genes provide a new and reliable prognostic model for NB related to MYCN.

Keywords: MYCN; bioinformatics analysis; neuroblastoma; prognostic model; qRT-PCR.

MeSH terms

  • 20-Hydroxysteroid Dehydrogenases / genetics
  • Adaptor Proteins, Signal Transducing / genetics
  • Biomarkers, Tumor / genetics*
  • Computational Biology*
  • Cyclic AMP-Dependent Protein Kinase Catalytic Subunits / genetics
  • Cytoskeletal Proteins / genetics
  • DNA Helicases / genetics
  • Gene Expression Regulation, Neoplastic
  • Humans
  • N-Myc Proto-Oncogene Protein / genetics*
  • Nerve Tissue Proteins / genetics
  • Neuroblastoma / diagnosis*
  • Neuroblastoma / genetics*
  • Prognosis
  • Real-Time Polymerase Chain Reaction*

Substances

  • Adaptor Proteins, Signal Transducing
  • Biomarkers, Tumor
  • Cytoskeletal Proteins
  • N-Myc Proto-Oncogene Protein
  • Nerve Tissue Proteins
  • PDE4DIP protein, human
  • 20-Hydroxysteroid Dehydrogenases
  • 3 alpha-beta, 20 beta-hydroxysteroid dehydrogenase
  • Cyclic AMP-Dependent Protein Kinase Catalytic Subunits
  • PRKACB protein, human
  • DNA Helicases
  • CHD5 protein, human