The expression and activation of eukaryotic translation initiation factor 4E (eIF4E) is associated with cell transformation and tumor initiation, but the functional role and the mechanism whereby it drives immune cell infltration in breast cancer (BRCA) remain uncertain. | Li et al. BMC Cancer 2021 21 1305 https s12885-021-09010-0 RESEARCH Open Access High expression of eIF4E is associated with tumor macrophage infiltration and leads to poor prognosis in breast cancer Fan Li1 Huizhi Sun1 2 Yue Li1 Xiaoyu Bai1 Xueyi Dong1 3 Nan Zhao1 3 Jie Meng1 3 Baocun Sun1 2 and Danfang Zhang1 3 Abstract Background The expression and activation of eukaryotic translation initiation factor 4E eIF4E is associated with cell transformation and tumor initiation but the functional role and the mechanism whereby it drives immune cell infiltra- tion in breast cancer BRCA remain uncertain. Methods Oncomine Timer and UALCAN were used to analyze the expression of eIF4E in various cancers. PrognoS- can Kaplan Meier plotter and GEPIA were utilized to analyze the prognostic value of eIF4E in select cancers. In vitro cell experiments were used to verify the role of eIF4E in promoting the progression of BRCA. ImmuCellAI and TIMER database were used to explore the relationship between eIF4E and tumor infiltrating immune cells. The expression of a macrophage marker CD68 and an M2-type marker CD163 was evaluated using immunohistochemistry in 50 invasive BRCA samples on tissue microarrays. The Human Protein Atlas HPA database was used to show the expression of eIF4E and related immune markers. LinkedOmics and NetworkAnalyst were used to build the signaling network. Results Through multiple dataset mining we found that the expression of eIF4E in BRCA was higher than that in normal tissues and patients with increased eIF4E expression had poorer survival and a higher cumulative recurrence rate in BRCA. At the cellular level BRCA cell migration and invasion were significantly inhibited after eIF4E expression was inhibited by siRNA. Immune infiltration analysis showed that the eIF4E expression level was significantly associ- ated with the tumor purity and immune infiltration levels of different immune cells in BRCA. The results from immu- nohistochemical .
