Eukaryotic translation initiation factor 4E family member 2 is a poor prognostic marker and associated with tumor microenvironment in hepatocellular carcinoma

Eukaryotic translation initiation factor 4E family member 2 (EIF4E2) has been increasingly recognized as an oncoprotein that is upregulated in multiple cancers. However, there are limited studies investigating its role in HCC. We first interrogated mRNA expression in TCGA and ICGC database. EIF4E2 mRNA and protein expression levels in HCC were confirmed using qRT-PCR and immunohistochemistry(IHC). The prognosis was determined by Kaplan-Meier method, alongside Cox regression models. Furthermore, we investigated the link between EIF4E2 expression and clinicopathological characteristics, as well as tumor immunity. We studied the correlation between EIF4E2 and drug sensitivity. Single-cell and spatial transcriptomic analysis of EIF4E2 in HCC was also performed. Finally, GSEA was performed to delineate the biological processes. Our analysis revealed upregulation of EIF4E2 expression in TCGA, ICGC, IHC and qRT-PCR. In HCC, elevated EIF4E2 expression was correlated with histologic grade and pathological stage. High expression of EIF4E2 portended an unfavorable outcome. Cox regression confirmed EIF4E2 as an independent prognostic indicator. EIF4E2 was associated with Th2 cells, TFH and NK CD56 bright cells. The relationship between EIF4E2 and immune checkpoint expression was observed. The patients with high expression of EIF4E2 were sensitive to sorafenib, Gemcitabine and cisplatin. Single-cell and spatial transcriptomic analysis confirmed the overexpression of EIF4E2 in HCC. Mechanistically, GSEA implicated EIF4E2 in pro-tumorigenic processes such as the cell cycle and DNA replication. EIF4E2 upregulation correlates with malignant clinical features of HCC; further functional studies are warranted to validate its oncogenic function.