Pancreatic adenocarcinoma (PAAD) is a highly aggressive malignant tumor with a poor prognosis. Integrin subunit genes (ITGs) serve as biomarkers for various types of cancers; however, to date, no prognostic research has been conducted on the ITGs in PAAD. This study aims to fill this gap by investigating the role of ITGs in PAAD prognosis.RNA-sequencing data, clinicopathological features, and survival information from The Cancer Genome Atlas (TCGA) database were sourced via GTEx. The GSE62452 data set was acquired from the Gene Expression Omnibus (GEO) database. A single-sample gene set enrichment analysis (ssGSEA) was first conducted to classify the PAAD samples from TCGA and GEO data sets with different ITG scores. A differential analysis was employed to identify the differentially expressed genes (DEGs) between the normal and PAAD samples, and between the high and low ITG score groups in both TCGA and GEO data sets.A total of 22 key differentially expressed ITGs (KDE-ITGs) were identified and enriched in eight Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, including the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway, focal adhesion, and the extracellular matrix (ECM)-receptor interaction. A prognostic model comprising the eight KDE-ITGs was established. Additionally, 2,371 DEGs were found between the high- and low-risk groups, which were mainly enriched in the Gene Ontology (GO) terms of cell morphogenesis and cytokine production, and KEGG pathways such as necroptosis, lysosome, and ferroptosis. Further, the proportions of T cells and cluster of differentiation 8 (CD8) T cells, and the expression levels of immune checkpoints, such as cluster of differentiation 274 (CD274) and lymphocyte activating gene 3 (LAG3), differed significantly between the two risk groups.The eight identified KDE-ITGs in PAAD were used to establish a new prognosis model, which might have clinical application, especially in immunotherapy.2024 AME Publishing Company. All rights reserved.