Profiling of the Prognostic Role of Extracellular Matrix-Related Genes in Neuroblastoma Using Databases and Integrated Bioinformatics
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods Used to Address the Significance of ECM Genes in NB
2.1. Gene Ontology, Expression and Mutational Profile of ECM-Related Genes, Their Correlation with Overall Survival, Risk Groups and Histology Status
2.2. cBioPortal, PCAT, MSigDB/BioGRID, STRING, GeneMANIA, Omicsnet and Cytoscape for Network Analysis for the Selected ECM-Related Genes
2.3. Validation of the Significance of the 12 ECM-Related Genes in Other Cancers
2.4. Correction for Multiple Testing
3. Results Supporting the Role of the 12 ECM Genes in NB
3.1. ECM-Related Genes Were Overexpressed in NB Patients, Showed Mutational Profiles, and Correlated with Risk Groups, MYCN Amplification, Histology and Overall Survival
3.2. cBioPortal, PCAT, MSigDB/ BioGRID, STRING, GeneMANIA, Omicsnet and Cytoscape Revealed Network Connectivity of the Selected ECM-Related Genes
3.3. Selected ECM-Related Genes Were Correlated with Patient Prognoses in Other Cancers
4. Discussion
5. Conclusions
Supplementary Materials
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
bFGF | Basic fibroblast growth factor |
CI | Confidence interval |
ECM | Extra-cellular matrix |
EFS | Event-free survival |
EMT | Epithelial-to-mesenchymal transition |
ER | Endoplasmic reticulum |
ERAD | Endoplasmic-associated degradation pathways |
ENA | European Nucleotide Archive |
FBS | Foetal bovine serum |
FDR | False discovery rate |
FISH | Fluorescent in situ hybridisation |
GSEA | Gene set enrichment analysis |
HCC | Hepatocellular carcinoma |
HR | Hazard ratio |
INRG | International Neuroblastoma Risk Group |
LIHC | Liver hepatocellular carcinoma |
LncRNAs | Long non-coding RNAs |
miRNAs | MicroRNAs |
NB | Neuroblastoma |
NSCLC | Non-small cell lung cancer |
OS | Overall survival |
RNAi | RNA interference |
RPKM | Reads per kilobase of transcripts per million |
PCAT | PDX for childhood therapeutics |
PDX | Patient-derived xenograft |
RFS | Recurrence-free survival |
SSBP1 | Single-stranded DNA-binding protein 1 |
TME | Tumour microenvironment |
TNBC | Triple-negative breast cancer |
TPM | Transcript per million |
UVM | Uveal Melanoma |
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Gene Name | Cancer Type | Examples of Roles in Tumourigenesis | Reference |
---|---|---|---|
HAS3 | Neuroblastoma | HAS3 potentiated melatonin-based differentiation in neuroblastoma | [35] |
LRP5 | Neuroblastoma | LRP5/6 protected SH-SY5Y cells against neurotoxicity induced by H2O2 | [36] |
RAMP2 | Neuroblastoma | RAMP2 expression was decreased in IMR-32 cells in hypoxic conditions | [37] |
RUVBL2 | Neuroblastoma | RUVBL2 potentiated cell death mediated by PCI-24781 in SK-N-DZ cells | [38] |
SSBP1 | Neuroblastoma | A gene involved in mitochondrial DNA replication which may have promising therapeutic roles | [39] |
Gene Name | Subcellular Localisation Database Attributed Role |
---|---|
AMBN | Ameloblastin, involved in the structural organisation and mineralisation of the enamel |
COLQ | Single-stranded homotrimer (collagen-like tail structure) of asymmetric acetylcholinesterase (AChE), attaches the catalytic subunits of asymmetric AChE to the basal lamina of the synapse |
ELFN1 | Fibronectin type III domain-containing protein 1 (extracellular leucine-rich repeat), a postsynaptic protein that regulated the circuit dynamics of the nervous system |
HAS3 | Hyaluronic acid synthase 3, essential for hyaluronan synthesis, that is a component of the ECM with structural roles |
HSPE1 | Heat shock protein family E, a co-chaperonin involved in mitochondrial protein transport and the assembly of macromolecules |
LMAN1 | Mannose-specific lectin, ER-Golgi intermediate protein, could recognise sugar residues in molecules and may be involved in recycling |
LRP5 | Low-density lipoprotein receptor-related protein 5 implicated in the Wnt-frizzled-LRP5-LRP6 complex that can instigate β-catenin signalling |
MUC6 | Mucin-6, oligomeric mucus/gel-forming; played a role in the cryoprotection of epithelial layers and may be implicated as cancer markers |
RAMP2 | Receptor activity-modifying protein 2, involved in transport to the plasma membrane |
RUVBL2 | A member of the RuvB family, RuvB like AAA ATPase 2, and is involved in the endoplasmic reticulum (ER)-associated degradation pathways (ERAD) which impact ER stress-triggered responses |
SSBP1 | Single-stranded DNA-binding protein, this protein binds to single-stranded DNA, may be involved in mitochondrial DNA replication |
UMOD | Involved in the synthesis of the apical membrane of epithelial cells and may be implicated in water barrier permeability, may also assist neutrophil migration |
Gene Name | Cancer Type | Examples of Roles in Tumourigenesis | Reference |
---|---|---|---|
AMBN | Osteosarcoma | AMBN promoted osteogenic differentiation by inactivating Src, AMBN induced tumour suppression and sensitivity to doxorubicin through the AMBN-Src-Stat3 axis | [46] |
HAS3 | Urothelial carcinoma | HAS3 downregulation was correlated with tumour grade, invasion and metastasis in urothelial carcinoma | [47] |
HSPE1 | Clear cell renal cell carcinoma (ccRCC) | HSPE1 was significantly downregulated in patient samples of ccRCC | [48] |
LMAN1 | Microsatellite instability (MSI)-high colorectal cell lines | LMAN1 displayed a high mutation frequency in microsatellite instability-high colorectal cancer cell lines | [49] |
LRP5 | Gastric Cancer | LRP5 promoted gastric cancer via the Wnt/β-catenin pathway | [50] |
MUC6 | Gastric Cancer | MUC6 promoter methylation led to downregulating of this gene that promoted gastric cancer progression | [51] |
RAMP2 | Lung cancer | RAMP2 downregulation in lung cancer was correlated with high tumour grade | [52] |
RUVBL2 | Hepatocellular carcinoma | RUVBL2 mRNA overexpression was correlated with reduced recurrence-free survival (RFS) in hepatocellular carcinoma | [45] |
SSBP1 | Triple-negative breast cancer (TNBC) | SSBP1 downregulation in TNBC promoted metastasis in both in vitro and in vivo models | [53] |
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Jahangiri, L. Profiling of the Prognostic Role of Extracellular Matrix-Related Genes in Neuroblastoma Using Databases and Integrated Bioinformatics. Onco 2022, 2, 85-112. https://doi.org/10.3390/onco2020007
Jahangiri L. Profiling of the Prognostic Role of Extracellular Matrix-Related Genes in Neuroblastoma Using Databases and Integrated Bioinformatics. Onco. 2022; 2(2):85-112. https://doi.org/10.3390/onco2020007
Chicago/Turabian StyleJahangiri, Leila. 2022. "Profiling of the Prognostic Role of Extracellular Matrix-Related Genes in Neuroblastoma Using Databases and Integrated Bioinformatics" Onco 2, no. 2: 85-112. https://doi.org/10.3390/onco2020007