Prognostic significance of MYCN related genes in pediatric neuroblastoma: a study based on TARGET and GEO datasets

Wang, Haiwei; Wang, Xinrui; Xu, Liangpu; Zhang, Ji; Cao, Hua

doi:10.1186/s12887-020-02219-1

Cited by 18 publications

(17 citation statements)

References 23 publications

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“…Previously, we had shown that neuroblastoma patients with MYCN ampli cation were associated with adverse prognosis and revealed the prognostic signi cance of MYCN target genes using TARGET dataset [7]. In the present study, we further tested the prognostic effects of age at initial neuroblastoma diagnosis in TARGET dataset.…”

Section: Resultsmentioning

confidence: 81%

“…Neuroblastoma patients with MYCN ampli cation are classi ed into high risk sub-group and are correlated with adverse prognosis [4][5][6]. Moreover, neuroblastoma patients with high expression levels of MYCN target genes [7] or MYCN signature [8] are also associated with unfavorable clinical outcomes. On the contrary, neuroblastoma patients without MYCN ampli cation are classi ed into low risk sub-group and are often had better clinical outcomes [4].…”

Section: Introductionmentioning

confidence: 99%

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Bioinformatic analysis of the inner heterogeneity within MYCN non-amplified pediatric neuroblastoma sub-group

Wang

et al. 2020

Preprint

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Background: Pediatric neuroblastoma is divided into MYCN amplified and MYCN non-amplified sub-groups. However, the extent of heterogeneity within MYCN amplified or non-amplified pediatric neuroblastoma is unclear.Methods: The prognostic significance of age and MYCN amplification was determined through multivariate cox regression and Kaplan-Meier survival analysis. MYCN non-amplified pediatric neuroblastoma patients were divided into different sub-consensuses using non-negative matrix factorization (NMF) based on the gene expression profiling. Genes particularly expressed in MYCN non-amplified younger neuroblastoma patients were identified using Therapeutically Applicable Research to Generate Effective Treatments (TARGET) and Gene Expression Omnibus (GEO) datasets. The prognostic effects of ALCAM, CACNA2D3, DST, EPB41L4A and KIFIB in MYCN non-amplified pediatric neuroblastoma patients were determined by Kaplan-Meier survival.Results: Age and MYCN amplification were independent prognostic factors in pediatric neuroblastoma. Compared with MYCN non-amplified older neuroblastoma patients, MYCN non-amplified younger neuroblastoma patients had better clinical outcomes. MYCN non-amplified pediatric neuroblastoma was divided into three sub-consensuses through NMF assay and each sub-consensus was with significantly different clinical outcomes. However, MYCN amplified pediatric neuroblastoma could not divide into sub-groups with different clinical outcomes by age or by NMF assay. ALCAM, CACNA2D3, DST, EPB41L4A and KIFIB were highly expressed in MYCN non-amplified younger neuroblastoma patients. Moreover, the high expression levels of ALCAM, CACNA2D3, DST, EPB41L4A or KIFIB were associated with the favorable prognosis of MYCN non-amplified neuroblastoma patients. We also found that DST was an independent prognostic factor in MYCN non-amplified neuroblastoma patients and MYCN non-amplified younger neuroblastoma patients with high DST expression levels had the best clinical overall survival.Conclusions: MYCN non-amplified neuroblastoma was a heterogeneous disease and could be divided into sub-groups based on age or the expression levels of ALCAM, CACNA2D3, DST, EPB41L4A or KIFIB. MYCN non-amplified younger neuroblastoma patients with high DST expression levels had the best clinical overall survival.

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Section: Resultsmentioning

confidence: 81%

Section: Introductionmentioning

confidence: 99%

Bioinformatic analysis of the inner heterogeneity within MYCN non-amplified pediatric neuroblastoma sub-group

Wang

et al. 2020

Preprint

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“…Bioinformatics analysis methods provide a new idea for the evaluation of the prognosis of NB patients. A number of models to predict the prognosis of NB, including MYCN-related signatures ( Wang et al, 2020 ), hypoxia gene signatures ( Fardin et al, 2010 ), and immune-based models ( Song et al, 2020 ), have been reported. A large number of studies have shown that GTs are related to cancer progression and can potentially serve as novel biomarkers ( Potapenko et al, 2010 ; Burchell et al, 2018 ; Tang et al, 2019 ).…”

Section: Discussionmentioning

confidence: 99%

Identification of a Glycosyltransferase Signature for Predicting Prognosis and Immune Microenvironment in Neuroblastoma

Sha

Han

Sun

et al. 2022

Front. Cell Dev. Biol.

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Neuroblastoma (NB) is one of the most common solid tumors in children. Glycosyltransferases (GTs) play a crucial role in tumor development and immune escape and have been used as prognostic biomarkers in various tumors. However, the biological functions and prognostic significance of GTs in NB remain poorly understood. The expression data from Gene Expression Omnibus (GEO) and Therapeutically Applicable Research to Generate Effective Treatments (TARGET) were collected as training and testing data. Based on a progression status, differentially expressed GTs were identified. We constructed a GTscore through support vector machine, least absolute shrinkage and selection operator, and Cox regression in NB, which included four prognostic GTs and was an independent prognostic risk factor for NB. Patients in the high GTscore group had an older age, MYCN amplification, advanced International Neuroblastoma Staging System stage, and high risk. Samples with high GTscores revealed high disialoganglioside (GD2) and neuron-specific enolase expression levels. In addition, a lack of immune cell infiltration was observed in the high GTscore group. This GTscore was also associated with the expression of chemokines (CCL2, CXCL9, and CXCL10) and immune checkpoint genes (cytotoxic T-lymphocyte–associated protein 4, granzyme H, and granzyme K). A low GTscore was also linked to an enhanced response to anti–PD-1 immunotherapy in melanoma patients, and one type of tumor was also derived from neuroectodermal cells such as NB. In conclusion, the constructed GTscore revealed the relationship between GT expression and the NB outcome, GD2 phenotype, and immune infiltration and provided novel clues for the prediction of prognosis and immunotherapy response in NB.

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“…ARMC6 is the target gene of MYCN and indicates a poor prognosis for patients with neuroblastoma (NB) ( Wang et al, 2020a ). The transcription factor MYCN forms a heterodimer with the related transcription factor MAX and binds to the E-box DNA consensus sequence together to regulate the transcription of specific target genes ( Beierle et al, 2007 ), including ARMC6 ( Mathelier et al, 2014 ).…”

Section: Functional Interactions Of the Armc Subfamily In Specific Diseasesmentioning

confidence: 99%

ARMC Subfamily: Structures, Functions, Evolutions, Interactions, and Diseases

Huang

Jiang

Gao

et al. 2021

Front. Mol. Biosci.

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Armadillo repeat-containing proteins (ARMCs) are widely distributed in eukaryotes and have important influences on cell adhesion, signal transduction, mitochondrial function regulation, tumorigenesis, and other processes. These proteins share a similar domain consisting of tandem repeats approximately 42 amino acids in length, and this domain constitutes a substantial platform for the binding between ARMCs and other proteins. An ARMC subfamily, including ARMC1∼10, ARMC12, and ARMCX1∼6, has received increasing attention. These proteins may have many terminal regions and play a critical role in various diseases. On the one hand, based on their similar central domain of tandem repeats, this ARMC subfamily may function similarly to other ARMCs. On the other hand, the unique domains on their terminals may cause these proteins to have different functions. Here, we focus on the ARMC subfamily (ARMC1∼10, ARMC12, and ARMCX1∼6), which is relatively conserved in vertebrates and highly conserved in mammals, particularly primates. We review the structures, biological functions, evolutions, interactions, and related diseases of the ARMC subfamily, which involve more than 30 diseases and 40 bypasses, including interactions and relationships between more than 100 proteins and signaling molecules. We look forward to obtaining a clearer understanding of the ARMC subfamily to facilitate further in-depth research and treatment of related diseases.

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Prognostic significance of MYCN related genes in pediatric neuroblastoma: a study based on TARGET and GEO datasets

Cited by 18 publications

References 23 publications

Bioinformatic analysis of the inner heterogeneity within MYCN non-amplified pediatric neuroblastoma sub-group

Bioinformatic analysis of the inner heterogeneity within MYCN non-amplified pediatric neuroblastoma sub-group

Identification of a Glycosyltransferase Signature for Predicting Prognosis and Immune Microenvironment in Neuroblastoma

ARMC Subfamily: Structures, Functions, Evolutions, Interactions, and Diseases

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