Effect of the TGF-b signaling pathway on spinal cord ependymoma: A study based on bioinformatics analysis and clinical trials.

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.