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Published on: July 22, 2020
Screening for genes and subnetworks associated with atypical teratoid/rhabdoid tumors using bioinformatics analysis
Gaowei Li1, Yuelong Wang1,2, Linjun Cai3
1Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
Abstract:
Objectives: Atypical teratoid/rhabdoid tumors (AT/RTs) are rare, fast-growing lesions of central nervous system and their prognosis is poor. Nowadays, multimodal managements, including surgery, chemotherapy and radiation therapy are advocated; however, low survival rate and severe neurocognitive toxicity of chemotherapy as well as the irreversible long-term sequelae of irradiation in infants and young children with AT/RTs are alarming. The aim of our study is to provide valid biological information for more tailored advance therapy for these lesions.Methods: Gene expression profile of GSE94349 was downloaded from GEO database and was analyzed using limma R package. Function and enrichment analyses of DEGs were performed based on DAVID database. PPI network construction, hub gene selection and module analysis were conducted in Cytoscape software.Results: In this study, 224 up-regulated genes and 572 down-regulated genes were selected as DEGs. The up-regulated genes were mainly enriched in molecular function and cell component, which mainly included protein binding and nucleus, respectively. The down-regulated DEGs were significantly involved in cell component such as plasma membrane and integral component of membrane. Cell cycle and retrograde endocannabinoid signaling were the main KEGG pathway of up and down DEGs, respectively. CDK1, CCNA2, CDC20, TOP2A were identified as hub genes and two significant network modules were also obtained.Conclusions: Our study may help to further understand the molecular characteristics and provide more tailored targets for future treatment of AT/RTs. Hub genes CDK1, CCNA2, CDC20, TOP2A as well as cell cycle signaling pathway may be new more tailored targets for future treatment of AT/RTs.
Insights
This study identifies key genes like CDK1 and CCNA2 involved in cell cycle regulation, offering potential new therapeutic targets for atypical teratoid/rhabdoid tumors (AT/RTs). These findings aim to improve treatment strategies for this rare central nervous system cancer.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Atypical teratoid/rhabdoid tumors (AT/RTs) are aggressive central nervous system cancers with poor prognoses.
- Current treatments like chemotherapy and radiation have significant toxicities, especially in young children.
Purpose of the Study:
- To identify novel molecular targets for improved AT/RT therapy.
- To understand the underlying gene expression profiles of AT/RTs.
Main Methods:
- Downloaded and analyzed gene expression data (GSE94349) using bioinformatics tools.
- Performed differential gene expression analysis, functional enrichment, and network analysis.
- Identified hub genes and significant molecular pathways.
Main Results:
- Identified 224 up-regulated and 572 down-regulated differentially expressed genes (DEGs).
- Up-regulated genes were enriched in cell cycle pathways; down-regulated genes in membrane-related functions.
- Identified CDK1, CCNA2, CDC20, and TOP2A as key hub genes.
Conclusions:
- The cell cycle pathway and identified hub genes represent potential therapeutic targets for AT/RTs.
- This research provides a molecular basis for developing more targeted and effective treatments.
- Further investigation into these targets could lead to improved outcomes for AT/RT patients.
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