Computational multi-omics integration suggests an association between LAMA3 expression, immune suppression, and metabolic programs in pancreatic ductal adenocarcinoma

Abstract Background Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy in which immune dysregulation and metabolic remodeling are common features. Laminin subunit alpha 3 (LAMA3), a component of laminin-332 involved in cell–ECM adhesion and integrin-linked signaling, has not been systematically characterized in PDAC in a multi-omics context. Methods We conducted an in silico integrative multi-omics analysis using bulk and single-cell transcriptomic datasets, together with WGCNA, functional enrichment, immune deconvolution, CNV inference, pseudotime trajectory analysis, and regulatory network modeling. Candidate upstream regulators were explored computationally, and molecular docking was performed for hypothesis generation. Results LAMA3 showed higher expression in PDAC compared with non-tumor controls and was associated with pathways related to cell adhesion, extracellular matrix organization/remodeling, and immune-related programs. In bulk deconvolution analyses, higher LAMA3 expression was associated with increased macrophage-related signatures and lower estimated CD8⁺T-cell infiltration. Single-cell analyses indicated predominant expression in epithelial populations and higher CNV activity in LAMA3-high states; LAMA3 expression also tended to increase along inferred pseudotime trajectories, consistent with more advanced malignant epithelial programs. Enrichment analyses further linked LAMA3-high tumors to cell-cycle-, p53-related, and metabolic gene sets. Regulatory modeling prioritized EP300 as a putative upstream transcriptional regulator, and docking analyses suggested a potential interaction between Prostaglandin J2 and EP300, supporting an indirect, hypothesis-generating therapeutic avenue. Conclusion This computational multi-omics study implicates LAMA3 as a candidate biomarker and a potential contributor to adhesion-associated tumor programs and an immunologically constrained microenvironment in PDAC. These findings are association-based and require experimental validation (e.g., functional perturbation and orthogonal immune profiling) before causal or therapeutic claims can be made.