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Integrated bioinformatic analysis unveils significant genes and pathways in the pathogenesis of supratentorial primitive neuroectodermal tumor.

ABSTRACT: Purpose:This study aimed to explore significant genes and pathways involved in the pathogenesis of supratentorial primitive neuroectodermal tumor (sPNET). Materials and methods:Gene expression profile of GSE14295 was downloaded from publicly available Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were screened out in primary sPNET samples compared with normal fetal and adult brain reference samples (sPNET vs fetal brain and sPNET vs adult brain). Pathway enrichment analysis of these DEGs was conducted, followed by protein-protein interaction (PPI) network construction and significant module selection. Additionally, transcription factors (TFs) regulating the common DEGs in the two comparison groups were identified, and the regulatory network was constructed. Results:In total, 526 DEGs (99 up- and 427 downregulated) in sPNET vs fetal brain and 815 DEGs (200 up- and 615 downregulated) in sPNET vs adult brain were identified. DEGs in sPNET vs fetal brain and sPNET vs adult brain were associated with calcium signaling pathway, cell cycle, and p53 signaling pathway. CDK1, CDC20, BUB1B, and BUB1 were hub nodes in the PPI networks of DEGs in sPNET vs fetal brain and sPNET vs adult brain. Significant modules were extracted from the PPI networks. In addition, 64 upregulated and 200 downregulated overlapping DEGs were identified in both sPNET vs fetal brain and sPNET vs adult brain. The genes involved in the regulatory network upon overlapping DEGs and the TFs were correlated with calcium signaling pathway. Conclusion:Calcium signaling pathway and several genes (CDK1, CDC20, BUB1B, and BUB1) may play important roles in the pathogenesis of sPNET.

SUBMITTER: Wang GY

PROVIDER: S-EPMC5894672 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Integrated bioinformatic analysis unveils significant genes and pathways in the pathogenesis of supratentorial primitive neuroectodermal tumor.

Wang Guang-Yu GY Li Ling L Liu Bo B Han Xiao X Wang Chun-Hua CH Wang Ji-Wen JW

OncoTargets and therapy 20180404

<h4>Purpose</h4>This study aimed to explore significant genes and pathways involved in the pathogenesis of supratentorial primitive neuroectodermal tumor (sPNET).<h4>Materials and methods</h4>Gene expression profile of GSE14295 was downloaded from publicly available Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were screened out in primary sPNET samples compared with normal fetal and adult brain reference samples (sPNET vs fetal brain and sPNET vs adult brain). Pa ...[more]

PMID: 29670360

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Project description:BackgroundEwing sarcoma/PNET is managed with treatment paradigms involving combinations of chemotherapy, surgery, and sometimes radiation. Although the 5-year survival rate of non-metastatic disease approaches 70%, those cases that are metastatic and those that recur have 5-year survival rates of less than 20%. Molecularly targeted treatments offer the potential to further improve treatment outcomes.MethodsA PUBMED search was performed from 1997 to 2011. Published literature that included the topic of the Ewing sarcoma/PNET was also referenced.ResultsInsulin-like growth factor-1 receptor (IGF-1R) antagonists have demonstrated modest single agent efficacy in phase I/II clinical trials in Ewing sarcoma/PNET, but have a strong preclinical rationale. Based on in vitro and animal data, treatment using antisense RNA and cDNA oligonucleotides directed at silencing the EWS-FLI chimera that occurs in most Ewing sarcoma/PNET may have potential therapeutic importance. However drug delivery and degradation problems may limit this therapeutic approach. Protein-protein interactions can be targeted by inhibition of RNA helicase A, which binds to EWS/FLI as part of the transcriptional complex. Tumour necrosis factor related apoptosis inducing ligand induction using interferon has been used in preclinical models. Interferons may be incorporated into future chemotherapeutic treatment paradigms. Histone deacetylase inhibitors can restore TGF-β receptor II allowing TFF-β signalling, which appears to inhibit growth of Ewing sarcoma/PNET cell lines in vitro. Immunotherapy using allogeneic natural killer cells has activity in Ewing sarcoma/PNET cell lines and xenograft models. Finally, cyclin dependent kinase inhibitors such as flavopiridol may be clinically efficacious in relapsed Ewing sarcoma/PNET.ConclusionPreclinical evidence exists that targeted therapeutics may be efficacious in the ESFT. IGF-1R antagonists have demonstrated efficacy in phase I/II clinical trials, although predicting responses remains a challenge. The future treatment of Ewing sarcoma/PNET is likely to be improved by these scientific advances.

Dataset Information

Integrated bioinformatic analysis unveils significant genes and pathways in the pathogenesis of supratentorial primitive neuroectodermal tumor.

Publications

Integrated bioinformatic analysis unveils significant genes and pathways in the pathogenesis of supratentorial primitive neuroectodermal tumor.

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