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Published on: July 22, 2020
Identification of key genes and molecular mechanisms associated with dedifferentiated liposarcoma based on
Hongliang Yu1, Dong Pei2, Longyun Chen2
1Department of Radiation Oncology, Jiangsu Cancer Hospital and Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing.
Background:
Dedifferentiated liposarcoma (DDLPS) is one of the most deadly types of soft tissue sarcoma. To date, there have been few studies dedicated to elucidating the molecular mechanisms behind the disease; therefore, the molecular mechanisms behind this malignancy remain largely unknown.
Materials And Methods:
Microarray profiles of 46 DDLPS samples and nine normal fat controls were extracted from Gene Expression Omnibus (GEO). Quality control for these microarray profiles was performed before analysis. Hierarchical clustering and principal component analysis were used to distinguish the general differences in gene expression between DDLPS samples and the normal fat controls. Differentially expressed genes (DEGs) were identified using the Limma package in R. Next, the enriched Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were obtained using the online tool DAVID (http://david.abcc.ncifcrf.gov/). A protein-protein interaction (PPI) network was constructed using the STRING database and Cytoscape software. Furthermore, the hub genes within the PPI network were identified.
Results:
All 55 microarray profiles were confirmed to be of high quality. The gene expression pattern of DDLPS samples was significantly different from that of normal fat controls. In total, 700 DEGs were identified, and 83 enriched GO terms and three KEGG pathways were obtained. Specifically, within the DEGs of DDLPS samples, several pathways were identified as being significantly enriched, including the PPAR signaling pathway, cell cycle pathway, and pyruvate metabolism pathway. Furthermore, the dysregulated PPI network of DDLPS was constructed, and 14 hub genes were identified. Characteristic of DDLPS, the genes CDK4 and MDM2 were universally found to be up-regulated and amplified in gene copy number.
Conclusion:
This study used bioinformatics to comprehensively mine DDLPS microarray data in order to obtain a deeper understanding of the molecular mechanism of DDLPS.
Insights
Dedifferentiated liposarcoma (DDLPS) is a deadly sarcoma. Bioinformatics analysis revealed significant gene expression differences, identifying key pathways and hub genes like CDK4 and MDM2, advancing understanding of this malignancy.
Area of Science:
- Oncology
- Genomics
- Bioinformatics
Background:
- Dedifferentiated liposarcoma (DDLPS) is an aggressive soft tissue sarcoma with poorly understood molecular underpinnings.
- Limited research exists on the molecular mechanisms driving DDLPS, hindering effective therapeutic strategies.
Purpose of the Study:
- To comprehensively analyze gene expression data from DDLPS samples.
- To identify differentially expressed genes (DEGs), enriched pathways, and key molecular players in DDLPS.
Main Methods:
- Utilized Gene Expression Omnibus (GEO) microarray data from 46 DDLPS samples and 9 normal fat controls.
- Applied hierarchical clustering, principal component analysis, Limma package for DEG identification, DAVID for pathway enrichment, and STRING/Cytoscape for network analysis.
- Identified hub genes within the protein-protein interaction (PPI) network.
Main Results:
- Confirmed significant differences in gene expression patterns between DDLPS and normal fat tissues.
- Identified 700 DEGs, 83 Gene Ontology (GO) terms, and 3 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, including PPAR signaling, cell cycle, and pyruvate metabolism.
- Constructed a dysregulated PPI network, identified 14 hub genes, and confirmed upregulation and amplification of CDK4 and MDM2.
Conclusions:
- Bioinformatic analysis of DDLPS microarray data provides deeper insights into its molecular mechanisms.
- Identified key molecular pathways and genes (CDK4, MDM2) crucial for DDLPS development and progression.
- This study lays the groundwork for future research into targeted therapies for DDLPS.
