Identification of MARK2, CCDC71, GATA2, and KLRC3 as candidate diagnostic genes and potential therapeutic targets for repeated implantation failure with antiphospholipid syndrome by integrated bioinformatics analysis and machine learning.

Background

Antiphospholipid syndrome (APS) is a group of clinical syndromes of thrombosis or adverse pregnancy outcomes caused by antiphospholipid antibodies, which increase the incidence of

Methods

To obtain differentially expressed genes (DEGs), we downloaded the APS and RIF datasets separately from the public Gene Expression Omnibus database and performed differential expression analysis. We then identified the common DEGs of APS and RIF. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed, and we then generated protein-protein interaction. Furthermore, immune infiltration was investigated by using the CIBERSORT algorithm on the APS and RIF datasets. LASSO regression analysis was used to screen for candidate diagnostic genes. To evaluate the diagnostic value, we developed a nomogram and validated it with receiver operating characteristic curves, then analyzed these genes in the Comparative Toxicogenomics Database. Finally, the Drug Gene Interaction Database was searched for potential therapeutic drugs, and the interactions between drugs, genes, and immune cells were depicted with a Sankey diagram.

Results

There were 11 common DEGs identified: four downregulated and seven upregulated. The common DEG analysis suggested that an imbalance of immune system-related cells and molecules may be a common feature in the pathophysiology of APS and RIF. Following validation, MARK2, CCDC71, GATA2, and KLRC3 were identified as candidate diagnostic genes. Finally, Acetaminophen and Fasudil were predicted as two candidate drugs.

Conclusion

Four immune-associated candidate diagnostic genes (MARK2, CCDC71, GATA2, and KLRC3) were identified, and a nomogram for RIF with APS diagnosis was developed. Our findings may aid in the investigation of potential biological mechanisms linking APS and RIF, as well as potential targets for diagnosis and treatment.

Informations de copyright

Copyright © 2023 Zhang, Ge, Zhang and La.

Déclaration de conflit d'intérêts

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.