AC005034.3/hsa-miR-126-5p/EIF3H axis: bioinformatics analysis, expression validation, and association with prognosis and immunosuppressive microenvironment in pancreatic adenocarcinoma

TL;DR

This study identifies a noncoding RNA pathway linked to EIF3H overexpression in pancreatic cancer, which is associated with poor prognosis and immune suppression.

Contribution

The study identifies the AC005034.3/hsa-miR-126-5p/EIF3H axis as a novel ncRNA-driven pathway in pancreatic adenocarcinoma.

Findings

EIF3H overexpression is associated with poor prognosis in pancreatic adenocarcinoma.

AC005034.3/hsa-miR-126-5p axis contributes to EIF3H upregulation in PAAD.

EIF3H expression correlates with immune infiltration and chemotherapeutic sensitivity in PAAD.

Abstract

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.

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.

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/EIF3H axis may serve as a promising prognostic biomarker and therapeutic target in PAAD.

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