DOK5 as an oncogenic mediator in gastric cancer: Mechanistic insights through bioinformatics and clinical validation

Gastric cancer (GC) exhibits metastasis-driven mortality, necessitating novel biomarkers. Although Docking Protein 5 ( DOK5 ), a tyrosine kinase substrate previously implicated in neuronal development and signaling cascades, remains mechanistically uncharacterized in GC. DOK5 's diagnostic and prognostic potential was evaluated via integrated The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) data mining. Utilizing 93 surgically resected specimens (2011–2015 retrospective cohort), we correlated DOK5 immunoreactivity with clinicopathological variables. Gene Set Enrichment Analysis (GSEA) elucidated pathway associations. DOK5 demonstrated significant tumoral overexpression versus normal mucosa, prognosticating reduced survival. Clinical validations confirmed diagnostic capabilities and TNM-stage associations. GSEA revealed that DOK5 expression positively correlated with epithelial-mesenchymal transition (EMT) and Notch signaling. DOK5 functions as a tumor-promoting factor in GC carcinogenesis, mechanistically facilitating malignant progression through EMT program activation and Notch signaling pathway engagement. Critically, DOK5 immunohistochemistry may serve as a clinically feasible biomarker to stratify high-risk gastric cancer patients during routine histopathology assessment. This establishes DOK5 as both a prognostic indicator and a therapeutic target in GC therapeutics.