High expression of eIF4E regulates immune cell infiltration and leads to poor prognosis in breast cancer

Background The expression and activation of Eukaryotic translation initiation factor 4E (eIF4E) is related to tumor transformation and genesis, but the functional role and the mechanism whereby it drives immune infiltration in breast cancer remain uncertain. Methods Multiple databases were used for assessing the expression and clinic-pathological features of eIF4E, after which ImmuCellAI and TIMER database were used to explore the relationship between eIF4E and immune infiltration and clinicopathological information were collected from clinical cases of breast cancer. Finally, the genes co-expressed with eIF4E were identified by LinkedOmics. These genes were analyzed protein interaction network and TF-miRNA interaction network by Networkanalyst, and enriched by GO and KEGG. The key genes of immune markers were functionally annotated. Results High expression of eIF4E was associated with poor overall survival (OS) and relapse-free survival (RFS) in breast cancer samples from multiple databases. It is notable that the expression of eIF4E is positively correlated with the infiltration of CD8+T cells, macrophages, neutrophils and dendritic cells. The expression of eIF4E is closely related to many immune markers in breast cancer. Immunohistochemical analysis showed that the patients with high expression of eIF4E related macrophage marker (CD68+) and M2 type marker (CD163+) in tumor stroma(TS) were significantly correlated with poor prognosis (P < 0.05). High infiltration density of CD163+ had significant difference in TNM staging compared with those with low(P < 0.05).Functional analysis of co-expressed genes showed that they were involved in the biological process of human immune response. GO analysis showed that co-expressed immune marker genes were involved in human immune response, adaptive immune response, macrophage activation, extracellular structure organization and regulation of DNA metabolism process. KEGG enrichment showed that it was involved in inflammatory bowel disease, cell adhesion molecule pathway, JAK-STAT signal pathway, T cell receptor signal pathway and so on. Conclusions These results suggest that high expression of eIF4E regulates immune cell infiltration, especially promotes macrophage M2 polarization by JAK/STAT6 and PI3K/AKT pathway, which is associated with poor prognosis of breast cancer patients. It is a valuable prognostic biomarker for breast cancer patients, and may be a potential therapeutic target in the future.