Diagnostic value and immune infiltration characterization of YTHDF2 as a critical m6A regulator in osteoarthritic
Ashuai Bian1,2, Changming Wang1,2, Haotian Zhang1,2
1Department of Orthopaedics, The Second Affiliated Hospital of Anhui Medical University, Hefei, 230601, Anhui, People's Republic of China.
Background:
N6-methyladenosine (m6A) is a universal RNA modification pattern regulated by multiple m6A regulators. In osteoarthritis (OA), m6A regulators influence disease progression by regulating cartilage degradation. However, the function of m6A regulators in synovial tissue remains unclear. In this work, we investigated the biological significance of m6A regulators in osteoarthritic synovitis.
Methods:
Datasets were acquired from Gene Expression Omnibus. Differential analysis of merged data identified the differentially expressed m6A regulators. Machine learning models were used to evaluate genetic importance. To predict disease risk, a nomogram was constructed based on above m6A regulators. Cluster analysis divided the OA sample into different subgroups. Immune infiltration revealed the immune m6A regulators, which were validated using clinical samples. Eventually, a competing endogenous RNA (ceRNA) network was constructed.
Results:
We acquired five differentially expressed m6A regulators and a random forest model. The nomogram accurately predicted disease risk. We identified 122 differentially expressed genes between two m6A subgroups. The analysis of immune infiltration showed that YTHDF2 was an immune-related m6A regulator closely related with macrophages. In clinical samples, the protein and mRNA contents of YTHDF2 were consistent with the results of bioinformatic analysis. The ceRNA network based on YTHDF2 revealed 75 lncRNA nodes and 19 miRNA nodes.
Conclusion:
YTHDF2 has a high diagnostic value in the synovitis of OA and significantly influences the immune status of patients. Hence, YTHDF2, a critical m6A regulator, may provide a biomarker for diagnosis and immune therapy of osteoarthritic synovitis.
Insights
N6-methyladenosine (m6A) regulators are key in osteoarthritis (OA) synovitis. YTHDF2, an m6A regulator, shows diagnostic value and impacts immune status, offering potential for OA diagnosis and immune therapy.
Area of Science:
- Molecular Biology
- Immunology
- Genetics
Background:
- N6-methyladenosine (m6A) is a crucial RNA modification regulated by m6A regulators.
- m6A regulators impact osteoarthritis (OA) progression by influencing cartilage degradation.
- The role of m6A regulators in synovial tissue in OA remains largely unexplored.
Purpose of the Study:
- To investigate the biological significance of m6A regulators in osteoarthritic synovitis.
- To identify key m6A regulators associated with OA synovitis and immune infiltration.
- To explore the diagnostic and therapeutic potential of m6A regulators in OA.
Main Methods:
- Acquired and analyzed Gene Expression Omnibus datasets.
- Utilized differential expression analysis and machine learning models to identify key m6A regulators.
- Constructed a nomogram for disease risk prediction and performed cluster analysis.
- Investigated immune infiltration and validated findings in clinical samples.
- Developed a competing endogenous RNA (ceRNA) network.
Main Results:
- Identified five differentially expressed m6A regulators and a predictive random forest model.
- Developed a nomogram with high accuracy for predicting OA disease risk.
- Discovered YTHDF2 as an immune-related m6A regulator associated with macrophages in OA synovitis.
- Validated YTHDF2 expression in clinical samples, consistent with bioinformatic predictions.
- Constructed a ceRNA network centered on YTHDF2, involving numerous lncRNA and miRNA nodes.
Conclusions:
- YTHDF2 demonstrates significant diagnostic value in osteoarthritic synovitis.
- YTHDF2 plays a critical role in modulating the immune status of OA patients.
- YTHDF2 represents a promising biomarker for the diagnosis and potential immune-based therapy of osteoarthritic synovitis.
