EIF4B expression in lung squamous cell carcinoma using bulk and single-cell transcriptomic profiling.

e20537 Background: Dysregulated translation initiation is a hallmark of cancer progression and therapeutic resistance. Eukaryotic initiation factor 4B (EIF4B) enhances cap-dependent translation by promoting mRNA recruitment and helicase activity within the eIF4F complex. While epithelial–mesenchymal transition (EMT) and drug resistance critically drive lung squamous cell carcinoma (LUSC) aggressiveness, the contribution of EIF4B to these processes remains unclear. Methods: EIF4B expression was analyzed using TCGA-LUSC bulk RNA-seq data and single-cell RNA-seq data (GSE148071). Tumor–normal expression differences were assessed, and correlations with EMT scores and drug-resistance markers (ABCB1, CD44, ALDH1A1) were evaluated using Spearman analysis. Differential expression and Hallmark gene set enrichment analyses were performed comparing EIF4B-high versus EIF4B-low tumors. Single-cell analyses mapped EIF4B expression across cellular subpopulations and assessed co-expression with EMT and stemness signatures. Results: EIF4B expression was significantly reduced in LUSC tumors compared with normal tissue (p < 0.001). Despite this global downregulation, EIF4B-high tumors demonstrated significantly elevated EMT scores (ρ = 0.16, p = 0.0001) and positive correlations with ABCB1 (ρ = 0.35), CD44 (ρ = 0.32), and ALDH1A1 (ρ = 0.22). Gene set enrichment analysis revealed activation of xenobiotic metabolism and coagulation pathways, alongside suppression of E2F and G2/M checkpoint programs. Single-cell profiling identified EIF4B enrichment within EMT-active epithelial and stem-like subpopulations, with significant correlations to cell-level EMT and resistance scores. Conclusions: Although globally downregulated in LUSC, EIF4B selectively marks mesenchymal and drug-resistant tumor subpopulations. Integrated bulk and single-cell analyses implicate EIF4B as a functional mediator of EMT-associated therapeutic resistance, highlighting its potential as a target to overcome treatment-refractory LUSC phenotypes.