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Screening Key Pathogenic Genes and Small Molecule Compounds for PNET
Abstract:
Primitive neuroectodermal tumors (PNET) are rare malignant tumors, but the mortality rate of the patients is extremely high. The aim of this study was to identify the hub genes and pathways involved in the pathogenesis of PNET and to screen the potential small molecule drugs for PNET. We extracted gene expression profiles from the Gene Expression Omnibus database and identified differentially expressed genes (DEGs) through Limma package in R. Two expression profiles (GSE14295 and GSE74195) were downloaded, including 33 and 5 cases separately. Four hundred sixty-eight DEGs (161 upregulated; 307 downregulated) were identified. Functional annotation and KEGG pathway enrichment of the DEGs were performed using DAVID and Kobas. Gene Ontology analysis showed the significantly enriched Gene Ontology terms included but not limited to mitosis, nuclear division, cytoskeleton, synaptic vesicle, syntaxin binding, and GABA A receptor activity. Cancer-related signaling pathways, such as DNA replication, cell cycle, and synaptic vesicle cycle, were found to be associated with these genes. Subsequently, the STRING database and Cytoscape were utilized to construct a protein-protein interaction and screen the hub genes, and we identified 5 hub genes (including CCNB1, CDC20, KIF11, KIF2C, and MAD2L1) as the key biomarkers for PNET. Finally, we identified potential small molecule drugs through CMap. Seven small molecule compounds, including trichostatin A, luteolin, repaglinide, clomipramine, lorglumide, vorinostat, and resveratrol may become potential candidates for PNET drugs.
Insights
This study identifies key genes like CCNB1 and CDC20 involved in primitive neuroectodermal tumors (PNET) and suggests potential drugs, offering hope for this rare cancer.
Area of Science:
- Oncology
- Genomics
- Bioinformatics
Background:
- Primitive neuroectodermal tumors (PNET) are rare and aggressive malignancies with high mortality rates.
- Understanding the molecular mechanisms driving PNET pathogenesis is crucial for developing effective treatments.
Purpose of the Study:
- To identify key genes (hub genes) and molecular pathways implicated in PNET development.
- To discover potential small molecule drug candidates for PNET treatment.
Main Methods:
- Analysis of gene expression profiles from the Gene Expression Omnibus (GEO) database.
- Identification of differentially expressed genes (DEGs) using Limma package in R.
- Functional annotation (Gene Ontology, KEGG pathways) and protein-protein interaction network construction (STRING, Cytoscape).
- Screening of potential small molecule drugs using the Connectivity Map (CMap).
Main Results:
- Identified 468 DEGs (161 upregulated, 307 downregulated) between PNET and normal samples.
- Enriched Gene Ontology terms included mitosis, nuclear division, and cytoskeleton-related functions.
- Key pathways associated with PNET include DNA replication, cell cycle, and synaptic vesicle cycle.
- Five hub genes (CCNB1, CDC20, KIF11, KIF2C, MAD2L1) were identified as potential biomarkers.
- Seven small molecule compounds (e.g., trichostatin A, luteolin, vorinostat) were identified as potential therapeutic candidates.
Conclusions:
- CCNB1, CDC20, KIF11, KIF2C, and MAD2L1 are critical hub genes in PNET pathogenesis.
- The identified small molecules show promise for future PNET drug development.
- This research provides valuable insights into PNET molecular mechanisms and potential therapeutic strategies.
