Functions, interactions and prognostic role of : a bioinformatics analysis.

Objective: To describe characteristics and reported mutations in endometrial cancer (EC) and analyze the impact of these mutations on the structure and function of the protein, as well as their relationship with the survival and prognosis of the disease.

Methods: We retrieved reported mutations for in EC from Catalogue of Somatic Mutations in Cancer database. We analyzed the most frequent mutations possible impact in the protein using HOPE server. We built a protein-protein network using Network Analyst, Cytoscape, and Network Analyzer plugin for topological analysis, enrichment analysis was performed using Gene Ontology: Biological processes. Clinical data was retrieved from cBioPortal database to compare overall survival between mutated (mut) and wild-type . Relation of mutational status of in EC and immune cell infiltration was analyzed using CIBERSORT algorithm in TIMER2.0 server.

Results: Thirty mutations in POLE were retrieved, most reported mutations were p.P286R, p.V411L and p.A456P, these mutations were likely to be pathogenic. Network analysis of POLE showed interaction of this protein in biological processes such as DNA repair, the cell proliferation cycle, and mechanisms of resistance to platinum. Immune infiltration analysis showed that T cell CD8+, T cell memory activated CD4+, T cell follicular helper, T cell gamma delta and macrophage M1 were more infiltrated in EC mut tumors.

Conclusion: Mutations in POLE might affect DNA polymerase epsilon function. These mutations also affect interactions with other proteins like proteins involved in different DNA repairing mechanisms. mutations may lead to platinum resistance, but they can also trigger an immune response that improves prognosis.