LAMA3 Orchestrates Immune Evasion and Metabolic Reprogramming in Pancreatic Ductal Adenocarcinoma: Insights from Multi-Omics Integration

Background Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy characterized by immune evasion and metabolic reprogramming. The role of laminin subunit alpha 3 (LAMA3), a key component in adhesion and signaling, remains poorly defined in PDAC. Methods We performed an integrative multi-omics analysis combining bulk and single-cell transcriptomics, WGCNA, CNV inference, pseudotime trajectory, enrichment analysis, and regulatory network modeling. Results LAMA3 was markedly upregulated in PDAC and enriched in pathways related to adhesion, extracellular matrix remodeling, and immune regulation. High LAMA3 expression correlated positively with immunosuppressive macrophages but negatively with CD8⁺ T-cell infiltration. Single-cell analysis revealed predominant epithelial expression, high CNV activity, and progressive upregulation along pseudotime, implicating a role in tumor evolution. Functional enrichment linked LAMA3 to cell cycle regulation, p53 signaling, and metabolic reprogramming. Regulatory modeling identified EP300 as an upstream transcriptional regulator, while molecular docking suggested indirect pharmacological targeting through Prostaglandin J2. Conclusion Our findings highlight LAMA3 as a central regulator of adhesion, immune evasion, and tumor progression in PDAC, supporting its potential as a diagnostic biomarker and therapeutic target.