High expression of eIF4E is associated with tumor macrophage infiltration and leads to poor prognosis in breast cancer

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 infiltration in breast cancer (BRCA) remain uncertain. Methods Oncomine, Timer and UALCAN were used to analyze the expression of eIF4E in various cancers. PrognoScan, 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 associated with the tumor purity and immune infiltration levels of different immune cells in BRCA. The results from immunohistochemical (IHC) staining further proved that the expression of CD68+ and CD163+ were significantly increased and correlated with poor prognosis in BRCA patients (P < 0.05). Finally, interaction network and functional enrichment analysis revealed that eIF4E was mainly involved in tumor-related pathways, including the cell adhesion molecule pathway and the JAK-STAT signaling pathway. Conclusions Our study has demonstrated that eIF4E expression has prognostic value for BRCA patients. eIF4E may act as an essential regulator of tumor macrophage infiltration and may participate in macrophage M2 polarization.

A novel m7G-related signature to predict prognosis and immune status in patients with hepatocellular carcinoma

“…The expression of EIF4E were overexpressed in various cancer types and interrelated with a worse outcome in multiple cancer [30]. EIF4E was found related to several cancers, such as breast cancer [31], prostate cancer [32] and skin squamous cell carcinoma [33]. Consistent with our ndings, Jiang et al reported that EIF4E expression was overexpressed in HCC samples and cell lines, and its overexpression was an independent predictor for overall survival and disease-free survival [34].…”

Identification and Characterization of an Ageing-Associated 13-lncRNA Signature That Predicts Prognosis and Immunotherapy in Hepatocellular Carcinoma

“…In the ARG-ST1 and ARG-ST2 subtypes with good prognosis, tumour suppressor immune cell infltration, for instance, B cells [38] and CD4 + T cells [39], was observed to be considerably increased. Moreover, the infltration of cancer-promoting immune cells, for example, M2 macrophages, was also increased simultaneously [40,41]. Tis fnding is not entirely consistent with previous studies.…”

Robust eIF4B levels undermine invasive growth and immune evasion mechanisms in murine triple negative breast cancer models

“…The upregulation of inhibitory costimulatory signaling in response to inflammatory cytokines (66) and the integrated stress response (ISR) (81) are prime examples. Altered eIF4E levels also impact the immune infiltration of breast tumors (82). Here we uncover an additional player that negatively impacts the upregulation of PD-L1 in response to the tumoricidal, proinflammatory cytokine IFNgamma.…”