Integrative multi-omics characterization of integrin alpha 11 in gastric cancer and identification of candidate therapeutic compounds

BACKGROUNDGastric cancer (GC) is a common malignancy of the digestive system worldwide and remains associated with an unfavorable overall prognosis.ITGA11 mediates cellextracellular matrix (ECM) interactions, yet its clinical relevance, potential biological mechanisms, and therapeutic targeting prospects in GC remain insufficiently characterized. AIMTo comprehensively evaluate the expression, clinicopathological associations, and prognostic value of ITGA11 in GC and examine its relationships with DNA methylation, ECM remodeling, the tumor immune microenvironment, and resistance-associated molecular features, and identify candidate ITGA11-targeting compounds. METHODSData from The Cancer Genome Atlas (TCGA), Gene Expression Profiling Interactive Analysis, UALCAN, the Clinical Proteomic Tumor Analysis Consortium, MethSurv, AlphaFold, and other public resources were integrated to assess ITGA11 expression, prognostic relevance, methylation, and protein structural features.The diagnostic performance of ITGA11 was externally validated in two independent Gene Expression Omnibus cohorts, GSE54129 and GSE26899.Protein-protein interaction analysis, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses, and Gene Set Enrichment Analysis (GSEA) were employed to investigate ITGA11-related differentially expressed genes and functional pathways.Tumor Immune Estimation Resource, single-sample GSEA, and CIBERSORT were employed to assess immune infiltration, and the associations of ITGA11 with immune checkpoint-related and chemotherapy resistance-associated genes were examined.Structure-based virtual candidates, but their direct binding and biological activity warrant experimental validation.