Expression Patterns of Immune Genes Reveal Heterogeneous Subtypes of High-Risk Neuroblastoma
Abstract
:1. Introduction
2. Results
2.1. Expression Patterns of NB-Specific Immune-Related Genes Stratify HR-NB Patients into Clinically Significant Subtypes
2.2. Thirty-Nine NB-Specific Differentiated Immune-Related Genes and Their Biological Characterization in UHR-NB and HR-NB Subtypes
2.3. Validating Four Upregulated Immune-Related Genes in UHR-NB with Additional Independent Cohorts
2.4. Differentiated Immune-Related Genes in UHR-NB Subtype and Their Biological Significance
3. Discussion
4. Materials and Methods
4.1. Datasets
4.1.1. RNA-Seq Data for Pediatric Pan-Cancer from TARGET
4.1.2. Neuroblastoma Gene Expression Data from TARGET
4.1.3. GSE49710 RNA-Seq Data
4.1.4. Other Neuroblastoma Patient Datasets from GEO:
- GSE19274 [27]: it includes the expression data of neuroblastoma primary tumors with the Illumina Human 6 version 2 expression l bead chip. There are 100 samples and total 19,937 genes. Clinical information including age, gender, stage, MYCN and PLOIDY status, and risk categories is available, but there is no patient survival information in this data.
- GSE45547 [28]: the expression profiles from 649 neuroblastoma tumors were originally generated using 44K oligonucleotide microarrays. There are a total of 19,320 genes in the data, and clinical information including age, gender, stage, and mycn status, and survival are available, but there is no risk stratification in the data.
- GSE73517 [20]: the RNA expression profiles of 105 primary neuroblastomas were originally generated with the k oligonucleotide microarrays. There are 105 NB samples and 19,320 genes available. Clinical metadata include age, stage, risk, MYCN status, and heterozygous deletions of 1p or 11q and gain of 17q.
- GSE85047 [29]: this is the expression profiles of 283 primary untreated neuroblastoma tumors with Affymetrix Human Exon 1.0 ST Array. There are 13,489 expressed genes. All of the tumor samples are fully annotated including patient age at diagnosis, overall and progression free survival and MYCN amplification status.
- GSE120572 [6]: the gene expression profiles of 394 NB samples were originally produced with Agilent-020382 Human Custom Microarray 44k. There are 30,853 genes (transcripts) in the data. Clinical metadata, including age, stage, MYCN, and TERT status, are available.
4.2. Methods
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
Abbreviations
HR-NB | high risk neuroblastoma |
UHR-NB | ultra-high risk neuroblastoma |
NB | neuroblastoma |
ALL | acute lymphoblastic leukemia |
AML | acute myeloid leukemia |
WT | Wilms tumor |
TARGET | tumor alterations relevant for genomics-driven therapy |
ADAM22 | A Disintegrin And Metalloproteinase Domain 22 |
GAL | Galanin And GMAP Prepropeptide |
KLHL13 | Kelch Like Family Member 13 |
TWIST1 | Twist Family BHLH Transcription Factor 1 |
OS | overall survival |
EFS | event-free survival |
MYCN | MYCN Proto-Oncogene, BHLH Transcription Factor. |
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Sample Availability: All gene expression datasets in this manuscript were downloaded from public domain. The software tools for data analysis will be posted on GitHub (www.github.com), and will be freely available to any investigator wishing to use them. |
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Liu, Z.; Grant, C.N.; Sun, L.; Miller, B.A.; Spiegelman, V.S.; Wang, H.-G. Expression Patterns of Immune Genes Reveal Heterogeneous Subtypes of High-Risk Neuroblastoma. Cancers 2020, 12, 1739. https://doi.org/10.3390/cancers12071739
Liu Z, Grant CN, Sun L, Miller BA, Spiegelman VS, Wang H-G. Expression Patterns of Immune Genes Reveal Heterogeneous Subtypes of High-Risk Neuroblastoma. Cancers. 2020; 12(7):1739. https://doi.org/10.3390/cancers12071739
Chicago/Turabian StyleLiu, Zhenqiu, Christa N. Grant, Lidan Sun, Barbara A. Miller, Vladimir S. Spiegelman, and Hong-Gang Wang. 2020. "Expression Patterns of Immune Genes Reveal Heterogeneous Subtypes of High-Risk Neuroblastoma" Cancers 12, no. 7: 1739. https://doi.org/10.3390/cancers12071739