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

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-relat...

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Autores principales: Ma, KeXin, Zhang, PeiPei, Xia, Yu, Dong, Lin, Li, Ying, Liu, Liu, Liu, YaJuan, Wang, YouJun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9685875/
https://www.ncbi.nlm.nih.gov/pubmed/36419120
http://dx.doi.org/10.1186/s12920-022-01400-y
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author Ma, KeXin
Zhang, PeiPei
Xia, Yu
Dong, Lin
Li, Ying
Liu, Liu
Liu, YaJuan
Wang, YouJun
author_facet Ma, KeXin
Zhang, PeiPei
Xia, Yu
Dong, Lin
Li, Ying
Liu, Liu
Liu, YaJuan
Wang, YouJun
author_sort Ma, KeXin
collection PubMed
description 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12920-022-01400-y.
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spelling pubmed-96858752022-11-25 A signature based on five immune-related genes to predict the survival and immune characteristics of neuroblastoma Ma, KeXin Zhang, PeiPei Xia, Yu Dong, Lin Li, Ying Liu, Liu Liu, YaJuan Wang, YouJun BMC Med Genomics Research 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12920-022-01400-y. BioMed Central 2022-11-23 /pmc/articles/PMC9685875/ /pubmed/36419120 http://dx.doi.org/10.1186/s12920-022-01400-y Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Ma, KeXin
Zhang, PeiPei
Xia, Yu
Dong, Lin
Li, Ying
Liu, Liu
Liu, YaJuan
Wang, YouJun
A signature based on five immune-related genes to predict the survival and immune characteristics of neuroblastoma
title A signature based on five immune-related genes to predict the survival and immune characteristics of neuroblastoma
title_full A signature based on five immune-related genes to predict the survival and immune characteristics of neuroblastoma
title_fullStr A signature based on five immune-related genes to predict the survival and immune characteristics of neuroblastoma
title_full_unstemmed A signature based on five immune-related genes to predict the survival and immune characteristics of neuroblastoma
title_short A signature based on five immune-related genes to predict the survival and immune characteristics of neuroblastoma
title_sort signature based on five immune-related genes to predict the survival and immune characteristics of neuroblastoma
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9685875/
https://www.ncbi.nlm.nih.gov/pubmed/36419120
http://dx.doi.org/10.1186/s12920-022-01400-y
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