Abstract

Background Pancreatic adenocarcinoma (PAAD) ranks among the most lethal human solid tumors, distinguished by its swift progression and limited effective treatment options. The eukaryotic translation initiation factor 3 subunit H (EIF3H) is postulated to be a critical factor in translational initiation, with emerging research indicating its potential involvement in promoting tumor invasion and metastasis. Nevertheless, the precise role of EIF3H within tumors remains insufficiently understood. Methods and Results Employing a comprehensive pan-cancer methodology, we conducted an analysis of datasets from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), ArrayExpress, and the International Cancer Genome Consortium (ICGC). This analysis systematically assessed the prognostic significance, clinical associations, signaling pathways, immune infiltration profiles, and chemotherapeutic sensitivity associated with EIF3H expression. Through a series of correlation, expression, and survival analyses, we identified noncoding RNAs (ncRNAs) that contribute to the upregulation of EIF3H in pancreatic adenocarcinoma (PAAD). Notably, we identified the AC005034.3/hsa-miR-126-5p axis as the most promising upstream ncRNA-related pathway influencing EIF3H expression in PAAD. The differential expression of these three genes between PAAD and normal pancreatic tissues was further validated using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry (IHC). Additionally, we demonstrated significant correlations between EIF3H expression and immune infiltration profiles, as well as chemotherapeutic sensitivity in PAAD. Furthermore, we constructed a protein-protein interaction (PPI) network and performed functional annotations involving EIF3H. Conclusion Our findings indicate that ncRNA-driven overexpression of EIF3H is associated with poor prognosis and tumor immune cell infiltration in PAAD, suggesting that the AC005034.3/hsa-miR-126-5p/