Abstract
BACKGROUND: Lung adenocarcinoma (LUAD), the predominant histologic subtype of non-small cell lung cancer (NSCLC), remains a leading cause of cancer-related mortality worldwide. However, stable biomarkers that simultaneously reflect prognosis and the tumor immune microenvironment are lacking. Low-density lipoprotein receptor-related protein 11 (LRP11), a member of the LDL receptor family, has been implicated in various cancers, but its role in LUAD remains unexplored. METHODS: In this study, we systematically evaluated the expression, clinical associations, and prognostic value of LRP11 in LUAD using transcriptomic data from TCGA and GEO platforms. Immune cell infiltration was analyzed using CIBERSORT and ssGSEA. Co-expression and pathway enrichment analyses were performed to investigate the underlying mechanisms, and a prognostic nomogram incorporating LRP11 was constructed and validated. New experimental data included: Western blotting (WB) and qRT-PCR to compare LRP11 expression levels in BEAS-2B, A549, and H1915 cells; immunohistochemical (IHC) staining of paired tissues for LRP11 localization; and LRP11 knockdown in A549/H1915 cells using two siRNAs to assess cell viability (CCK-8), migration (scratch assay), invasion (Transwell assay), and clonogenic ability. RESULTS: LRP11 was stably overexpressed in LUAD and was significantly associated with advanced pathological stage, distant metastasis, and poor survival outcomes. The prognostic nomogram incorporating LRP11 significantly improved the prediction of 1-, 3-, and 5-year survival. Immune analysis revealed that high LRP11 expression was associated with a decrease in CD8⁺ T cells and dendritic cells, while Tregs and M2 macrophages were enriched, indicating an immunosuppressive microenvironment. Functional enrichment analyses suggested that LRP11 is involved in RNA processing and antigen presentation pathways. Experimental data showed that LRP11 protein and mRNA levels were significantly elevated in A549/H1915 cells and LUAD tissues. LRP11 knockdown suppressed cell viability, reduced wound healing and transmembrane invasion, and decreased colony formation. CONCLUSION: LRP11 is upregulated in LUAD and is associated with immune suppression and poor prognosis. In vitro functional assays support its pro-tumorigenic role. LRP11 holds potential as both a prognostic and immune-related biomarker in LUAD, with promise as a therapeutic target, warranting further mechanistic studies and clinical research. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12672-025-03821-4.