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Published on: March 18, 2022
Identification of Potential Therapeutic Target Genes in Osteoarthritis
Yang Hu1, Yinteng Wu1, Fu Gan2
1Department of Orthopedics, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China.
Objective:
Osteoarthritis (OA), also known as joint failure, is characterized by joint pain and, in severe cases, can lead to loss of joint function in patients. Immune-related genes and immune cell infiltration play a crucial role in OA development. We used bioinformatics approaches to detect potential diagnostic markers and available drugs for OA while initially exploring the immune mechanisms of OA.
Methods:
The training set GSE55235 and validation set GSE51588 and GSE55457 were obtained from the Gene Expression Omnibus (GEO) database and differentially expressed genes (DEGs) were identified by the limma package. Gene set enrichment analysis (GSEA) was performed on the GSE55235 dataset using the cluster profiler package. At the same time, DEGs were analyzed by gene ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG). In addition, protein-protein interaction (PPI) analysis was performed on the common DEGs of the three datasets using the STRING database. Proteins with direct linkage were identified as hub genes, and the relation of hub genes was subsequently analyzed using the GOSemSim package. Hub genes' expression profiles and diagnostic capabilities (ROC curves) were analyzed and validated using three datasets. In addition, we performed RT-qPCR to validate the levels of hub genes. The immune microenvironment was analyzed using the CIBERSORT package, and the relationship between hub genes and immune cells was evaluated. In addition, we used a linkage map (CMAP) database to identify available drug candidates. Finally, the GSEA of hub genes was used to decipher the potential pathways corresponding to hub genes.
Results:
Three hub genes (CX3CR1, MYC, and TLR7) were identified. CX3CR1 and TLR7 were highly expressed in patients with OA, whereas the expression of MYC was low. The results of RT-qPCR validation were consistent with those obtained using datasets. Among these genes, CX3CR1 and TLR7 can be used as diagnostic markers. It was found that CX3CR1, MYC, and TLR7 affect the immune microenvironment of OA via different immune cells. In addition, we identified a potential drug for the treatment of OA. Altogether, CX3CR1, MYC, and TLR7 affect the immune response of OA through multiple pathways.
Conclusion:
CX3CR1, MYC, and TLR7 are associated with various immune cells and are the potential diagnostic markers and therapeutic targets for OA.
Insights
Three key genes, CX3CR1, MYC, and TLR7, were identified as potential diagnostic markers for osteoarthritis (OA). These genes influence the immune microenvironment and offer therapeutic targets for OA treatment.
Area of Science:
- Immunology
- Genetics
- Bioinformatics
Background:
- Osteoarthritis (OA) is characterized by joint pain and loss of function.
- Immune-related genes and immune cell infiltration are critical in OA development.
Purpose of the Study:
- Identify potential diagnostic markers for OA.
- Explore the immune mechanisms underlying OA.
- Discover available drug candidates for OA treatment.
Main Methods:
- Utilized bioinformatics approaches on Gene Expression Omnibus (GEO) datasets (GSE55235, GSE51588, GSE55457).
- Identified differentially expressed genes (DEGs) and performed Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA).
- Analyzed protein-protein interactions (PPI) to identify hub genes (CX3CR1, MYC, TLR7) and their association with immune cells via CIBERSORT and CMAP databases.
Main Results:
- Identified three hub genes: CX3CR1, MYC, and TLR7.
- CX3CR1 and TLR7 showed high expression in OA patients, while MYC expression was low.
- CX3CR1 and TLR7 demonstrated diagnostic potential for OA, and all three genes were linked to the OA immune microenvironment.
Conclusions:
- CX3CR1, MYC, and TLR7 are associated with immune cells and serve as potential diagnostic markers and therapeutic targets for OA.
- These genes influence OA's immune response through multiple pathways, offering new avenues for treatment.
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