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Effect of the TGF-b signaling pathway on spinal cord ependymoma: A study based on bioinformatics analysis and
Yan-Dong Fan1, Man-Li Zhu2, Mamutijiang Muertizha1
1Department of Neurosurgery, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang 830011, China.
Abstract:
This study aimed to identify potential therapeutic targets for spinal cord ependymoma (SCE) and key signaling pathways associated with the transforming growth factor b (TGF-b) signaling pathway through bioinformatics analysis, molecular biology validation, and clinical characteristics. Differentially expressed genes (DEGs) in SCE were identified using the limma package in R, and a Venn diagram was created to obtain the intersection of TGF-b signaling pathway-related genes and DEGs. Next, the clusterProfiler package was employed for enrichment analysis of Gene Ontology and Kyoto Encyclopedia of Genes and Genomes. Also, a protein-protein interaction network of DEGs was constructed using the Search Tool for the Retrieval of Interacting Genes/Proteins website, and Cytoscape was used to visualize and screen the top 20 key genes. Additionally, quantitative real-time polymerase chain reaction and western blot were used to validate the mRNA and protein expression levels, respectively, of SMAD4, TGFB1, and TGFB receptor 1 (TGFBR1) in clinical samples. A total of 61 differentially expressed TGF-b signaling pathway-related genes were associated with 1) biological processes, such as the transmembrane receptor protein serine/threonine kinase signaling pathway, TGF-b receptor signaling pathway, and pathway-restricted SMAD protein phosphorylation; 2) cell components, such as the plasma membrane signaling receptor complex and collagen-containing extracellular matrix; and 3) molecular function, such as SMAD binding, growth factor binding, and cytokine binding. The protein-protein interaction network consisted of 57 nodes and 339 edges, and three key genes (SMAD4, TGFB1, and TGFBR1) were screened. The TGF-b and Hippo signaling pathways may have potential roles in SCE progression, and SMAD4, TGFB1, and TGFBR1 are potential key genes.
Insights
This study identifies key genes and pathways in spinal cord ependymoma (SCE). SMAD4, TGFB1, and TGFBR1 are highlighted as potential therapeutic targets for this rare tumor.
Area of Science:
- Oncology
- Molecular Biology
- Bioinformatics
Background:
- Spinal cord ependymoma (SCE) is a rare tumor requiring identification of therapeutic targets.
- The transforming growth factor beta (TGF-b) signaling pathway is implicated in various cancers.
Purpose of the Study:
- To identify potential therapeutic targets for SCE.
- To elucidate key signaling pathways, particularly TGF-b, involved in SCE pathogenesis.
- To validate potential therapeutic targets using molecular and clinical data.
Main Methods:
- Bioinformatics analysis of differentially expressed genes (DEGs) in SCE.
- Utilized R packages (limma, clusterProfiler) for gene expression and pathway enrichment analysis.
- Constructed protein-protein interaction networks and validated key genes (SMAD4, TGFB1, TGFBR1) via qPCR and Western blot.
Main Results:
- Identified 61 differentially expressed TGF-b signaling pathway-related genes associated with specific biological processes, cellular components, and molecular functions.
- A protein-protein interaction network revealed SMAD4, TGFB1, and TGFBR1 as key genes.
- Validation confirmed elevated mRNA and protein levels of SMAD4, TGFB1, and TGFBR1 in clinical SCE samples.
Conclusions:
- The TGF-b signaling pathway plays a significant role in SCE progression.
- SMAD4, TGFB1, and TGFBR1 represent promising therapeutic targets for spinal cord ependymoma.
