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Targeted RNA Sequencing Assay to Characterize Gene Expression and Genomic Alterations
Published on: August 4, 2016
Identification of target genes of cediranib in alveolar soft part sarcoma using a gene microarray
Wenhua Jiang1,2, Pengfei Liu3, Xiaodong Li2
1Department of Radiotherapy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Sino-US Center of Lymphoma and Leukemia, Tianjin 300060, P.R. China.
Abstract:
The aim of the present study was to identify the target genes of cediranib and the associated signaling pathways in alveolar soft part sarcoma (ASPS). A microarray dataset (GSE32569) was obtained from the Gene Expression Omnibus database. The R software package was used for data normalization and screening of differentially expressed genes (DEGs). The Database for Annotation, Visualization and Integrated Discovery was used to perform Gene Ontology analysis. Gene Set Enrichment Analysis was performed to obtain the up- and downregulated pathways in ASPS. The Distant Regulatory Elements of co-regulated genes database was used to identify the transcription factors (TFs) that were enriched in the signaling pathways. A protein-protein interaction (PPI) network was constructed using the Search Tool for the Retrieval of Interacting Genes/Proteins database and was visualized using Cytoscape software. A total of 71 DEGs, including 59 upregulated genes and 12 downregulated genes, were identified. Gene sets associated with ASPS were enriched primarily in four signaling pathways: The phenylalanine metabolism pathway, the mitogen-activated protein kinase (MAPK) signaling pathway, the taste transduction pathway and the intestinal immune network for the production of immunoglobulin A. Furthermore, 107 TFs were identified to be enriched in the MAPK signaling pathway. Certain genes, including those coding for Fms-like tyrosine kinase 1, kinase insert domain receptor, E-selectin and platelet-derived growth factor receptor D, that were associated with other genes in the PPI network, were identified. The present study identified certain potential target genes and the associated signaling pathways of cediranib action in ASPS, which may be helpful in understanding the efficacy of cediranib and the development of new targets for cediranib.
Insights
This study identified key genes and signaling pathways, including the MAPK pathway, targeted by cediranib in alveolar soft part sarcoma (ASPS). Findings may guide future cediranib efficacy studies and new therapeutic target development.
Area of Science:
- Oncology
- Molecular Biology
- Genomics
Background:
- Alveolar soft part sarcoma (ASPS) is a rare cancer.
- Cediranib is a targeted therapy with potential applications in ASPS.
- Understanding cediranib's molecular targets in ASPS is crucial for optimizing treatment.
Purpose of the Study:
- To identify cediranib's target genes in ASPS.
- To elucidate the associated signaling pathways affected by cediranib in ASPS.
- To provide insights for developing novel therapeutic strategies for ASPS.
Main Methods:
- Utilized a microarray dataset (GSE32569) for gene expression analysis.
- Employed R software for data normalization and differential gene expression analysis.
- Performed Gene Ontology, Gene Set Enrichment Analysis, and constructed a protein-protein interaction network.
Main Results:
- Identified 71 differentially expressed genes (DEGs) in ASPS, with 59 upregulated and 12 downregulated.
- Discovered enrichment in four key signaling pathways: phenylalanine metabolism, mitogen-activated protein kinase (MAPK), taste transduction, and immunoglobulin A production.
- Identified 107 transcription factors enriched in the MAPK signaling pathway and several potential cediranib target genes within the protein-protein interaction network.
Conclusions:
- Cediranib targets specific genes and pathways in ASPS, notably the MAPK signaling pathway.
- The identified targets and pathways offer potential for understanding cediranib's efficacy.
- This research may facilitate the development of new therapeutic targets for ASPS treatment.

