A signature based on five immune-related genes to predict the survival and immune characteristics of neuroblastoma

KeXin Ma; PeiPei Zhang; Yu Xia; Lin Dong; Ying Li; Liu Liu; YaJuan Liu; YouJun Wang

doi:10.1186/s12920-022-01400-y

A signature based on five immune-related genes to predict the survival and immune characteristics of neuroblastoma

BMC Med Genomics. 2022 Nov 23;15(1):242. doi: 10.1186/s12920-022-01400-y.

Authors

KeXin Ma¹, PeiPei Zhang², Yu Xia¹, Lin Dong¹, Ying Li¹, Liu Liu¹, YaJuan Liu¹, YouJun Wang³

Affiliations

¹ Department of Pediatrics, The Fifth Affiliated Hospital of Zhengzhou University, No. 3 Kangfuqian Street, Zhengzhou, China.
² Department of Neonatology, Children's Hospital, Capital Institute of Pediatrics, Beijing, China.
³ Department of Pediatrics, The Fifth Affiliated Hospital of Zhengzhou University, No. 3 Kangfuqian Street, Zhengzhou, China. wyjerke@outlook.com.

Abstract

Background: MYCN amplification (MNA) has been proved to be related to poor prognosis in neuroblastoma (NBL), but the MYCN-related immune signatures and genes remain unclear.

Methods: Enrichment analysis was used to identify the significant enrichment pathways of differentially expressed immune-related genes (DEIRGs). Weight gene coexpression network analysis (WGCNA) was applied to reveal the correlation between these DEIRGs and MYCN status. Univariate and multivariate Cox analyses were used to construct risk model. The relevant fractions of immune cells were evaluated by CIBERSORT and single-sample gene set enrichment analysis (ssGSEA).

Results: Five genes, including CHGA, PTGER1, SHC3, PLXNC1, and TRIM55 were enrolled into the risk model. Kaplan-Meier survival analysis and receiver operating characteristic (ROC) curve showed that our model performed well in predicting the outcomes of NBL (3-years AUC = 0.720, 5-year AUC = 0.775, 10-years AUC = 0.782), which has been validated in the GSE49711 dataset and the E-MTAB-8248 dataset. By comparing with the tumor immune dysfunction and exclusion (TIDE) and tumor inflammation signature (TIS), we further proved that our model is reliable. Univariate and multivariate Cox regression analyses indicated that the risk score, age, and MYCN can serve as independent prognostic factors in the E-MATB-8248. Functional enrichment analysis showed the DEIRGs were enriched in leukocyte adhesion-related signaling pathways. Gene set enrichment analysis (GSEA) revealed the significantly enriched pathways of the five MYCN-related DEIRGs. The risk score was negatively correlated with the immune checkpoint CD274 (PD-L1) but no significant difference with the TMB. We also confirmed the prognostic value of our model in predicting immunotherapeutics.

Conclusion: We constructed and verified a signature based on DEIRG that related to MNA and predicted the survival of NBL based on relevant immune signatures. These findings could provide help for predicting prognosis and developing immunotherapy in NBL.

Keywords: Immune-related gene; MYCN amplification; Neuroblastoma; Prognosis.

MeSH terms

Biomarkers, Tumor / genetics
Gene Expression Regulation, Neoplastic*
Humans
N-Myc Proto-Oncogene Protein / genetics
Neuroblastoma* / genetics
Prognosis

Substances

Biomarkers, Tumor
N-Myc Proto-Oncogene Protein