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In Vitro Tumor Cell Rechallenge For Predictive Evaluation of Chimeric Antigen Receptor T Cell Antitumor Function
Published on: February 27, 2019
WGCNA and integrative network analysis identify CHRNA5 and CTLA4 as potential therapeutic targets against
Trishla Bhatnagar1, Madiha Haider1, Mohd Yasir Khan1
1Department of Biotechnology, Jamia Millia Islamia, New Delhi, India 110025.
Abstract:
Angiosarcomas are a type of soft-tissue sarcoma characterized by aggressive malignant tumors originating from endothelial cells of blood vessels or lymphatic vessels. Limited studies have been done to explore the molecular pathophysiology of the disease, with rather limited studies involving transcriptomic analyzes. This study was undertaken to identify the shared molecular signatures and gene modules associated with angiosarcomas of various origin. Transcriptomic data analysis of publicly available data was done followed by WGCNA to identify shared signature gene modules. The Maximal Clique Centrality algorithm was applied to gene modules, and unclustered network analysis was conducted on differentially expressed genes to identify true hub genes. The expression of candidate genes in various cancer types was analyzed using GEPIA. WGCNA analysis identified five significant modules, with the most enriched module being associated with angiogenesis and cell junction regulators. The intersection of true hub genes from MCC analysis of WGCNA modules and high-degree nodes from an unclustered network revealed eight consistently overexpressed genes in all angiosarcoma samples.Among the eight enriched genes, CHRNA5 and CTLA4, are exclusively overexpressed in angiosarcoma and not in other cancers of the same tissue origin, with significant drug-protein interactions suggesting their potential as therapeutic targets.
Insights
This study identified key molecular signatures in angiosarcomas, revealing eight consistently overexpressed genes. CHRNA5 and CTLA4 show potential as targeted therapies for this aggressive soft-tissue sarcoma.
Area of Science:
- Oncology
- Molecular Biology
- Genomics
Background:
- Angiosarcomas are aggressive soft-tissue sarcomas originating from endothelial cells.
- Limited research exists on their molecular pathophysiology, particularly transcriptomic analyses.
Purpose of the Study:
- To identify shared molecular signatures and gene modules in angiosarcomas of diverse origins.
- To uncover potential therapeutic targets through gene expression analysis.
Main Methods:
- Transcriptomic data analysis of public datasets.
- Weighted Gene Co-expression Network Analysis (WGCNA) to identify gene modules.
- Maximal Clique Centrality (MCC) and unclustered network analysis to identify hub genes.
- Gene Expression Profiling Interactive Analysis (GEPIA) for cross-cancer expression analysis.
Main Results:
- WGCNA identified five significant modules, with the most enriched related to angiogenesis and cell junction regulation.
- Eight consistently overexpressed genes were identified across all angiosarcoma samples.
- CHRNA5 and CTLA4 were found to be exclusively overexpressed in angiosarcomas compared to other cancers.
- Significant drug-protein interactions were noted for these candidate genes.
Conclusions:
- Shared molecular signatures and gene modules are associated with angiosarcomas.
- CHRNA5 and CTLA4 represent promising, angiosarcoma-specific therapeutic targets.
- Further investigation into these genes could lead to novel treatment strategies for angiosarcoma.
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