Analysis of tumorigenesis and immunological role of LTBP2: a potential predictor for immunotherapy

Latent Transforming Growth Factor-β-1 Binding Protein-2 (LTBP-2), a member of the LTBP-fibrillin superfamily of extracellular matrix proteins, has been implicated in promoting TGF-β expression and secretion. However, its precise role in tumorigenesis remains ambiguous. This study comprehensively investigates the potential impact of LTBP2 on patient prognosis and response to immune therapy across various cancer types. Method We analyzed LTBP2 expression in tumor versus adjacent normal tissues and its correlation with survival outcomes across different cancers using the GEPIA and Sangerbox databases. The association between LTBP2 expression and tumor grade, stage, molecular subtypes, and TGF-β expression was assessed through TISIDB, Sangerbox, and TIMER2.0 databases. We also explored LTBP2's relationship with immune checkpoint (ICP) genes, tumor mutational burden (TMB), microsatellite instability (MSI), and immune cell infiltration in tumors using the Sangerbox database. Receiver Operating Characteristic (ROC) curves and Mann-Whitney tests were employed to evaluate the link between immune checkpoint blockade therapy response and LTBP2 expression. GeneMANIA and GEPIA databases were utilized for identifying LTBP2-related genes and binding proteins, while Sangerbox facilitated functional and pathway enrichment analysis. Results LTBP2 was differentially expressed in most cancer types compared to adjacent normal tissues. High LTBP2 expression correlated with poor prognosis in various cancers from The Cancer Genome Atlas (TCGA) dataset. Correlations were found between LTBP2 expression and TMB, MSI, ICP genes, and tumor immune cell infiltration across multiple cancer types. LTBP2 expression was positively associated with TGF-β levels and infiltration of cancer-associated fibroblasts (CAFs) in nearly all tumor types. Diverse molecular subtypes of multiple tumors also exhibited differential LTBP2 expression. ROC and Mann-Whitney tests indicated that LTBP2 could predict the outcome of immune checkpoint blockade therapy in GBMLGG, STAD, ESCA, and SKCM. Functional enrichment analysis revealed LTBP2's involvement in vascular development, cell adhesion, extracellular matrix, and TGF-β, RAS, PI3K/AKT signaling pathways in tumors. Conclusion Our findings indicate that LTBP2 potentially plays a significant role in tumor immunity, tumorigenesis, and treatment efficacy. LTBP2 emerges as a prospective therapeutic target and may influence the response to tumor immune checkpoint blockade therapy.