dentification of the Potential Role of Anoikis in Etiopathogenesis of Lymphedema Through Bioinformatics Analyzes

Lymphedema results from excess fluid accummulation in the interstitial space due to impaired lymphatic drainage. Although genes and mutations in the etiology of primary lymphedema, which arises from developmental defects in the lymphatic system, have been identified, the molecular etiopathogenesis of lymphedema is unknown. In this study, it is tried to determine the molecular mechanisms involved in the etiopathogenesis of lymphedema via bioinformatics analyzes based on the list of genes associated with lymphedema. 69 genes whose mutations are associated with lymphedema in the Human Phenotype Ontology (HPO) database, were identified. Gene set enrichment analyzes (GSEA) were performed using this gene list and Enrichr tool. GSEA results using Gene Ontology (GO) database revealed that“Anoikis” (GO:0043276) and “Focal adhesion” (GO:0005925) mechanisms were among the top 10 most enriched terms (adjusted p values were 2.29x10-6 and 3.3x10-3, respectively). By using the Apoptosis and Focal Adhesion pathways in the Kyoto Encyclopedia of Genes and Genomes (KEGG) database, pathway maps with proteins enriched in terms were prepared. Finally, hsa-miR-451a and hsa- miR-494-3p were determined to target transcripts in these pathways (adjusted p values 3.58x10-6 and 6.42x10-6, respectively). As a result, with this study, data were obtained showing that anoikis, a form of cell death that occurs when the connections of cells attached to the extracellular environment are broken, may be associated with the emergence of lymphedema, and that hsa-miR-451a and hsa-miR-494-3p may have a role in the etiology of lymphedema.