Lipopolysaccharide-Binding Protein (LBP): A Prognostic Biomarker for Gastric Cancer Linked to Immune Infiltration

Abstract Background: Gastric cancer, characterized by increasing incidence and mortality rates worldwide, presents significant challenges due to the absence of effective early detection and screening methodologies. This limitation impedes timely therapeutic interventions, highlighting the necessity for novel biomarker discovery. Among potential candidates, Lipopolysaccharide-Binding Protein (LBP), implicated in several cancer types including lung, colon, and cervical cancers, emerges as a noteworthy focus. Despite its established involvement, LBP's specific contributions and mechanisms in gastric cancer require elucidation, especially considering the disease's distinct biological and pathological characteristics. Methods: This Study leverages data from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and Human Protein Atlas (HPA) to scrutinize LBP's mRNA and protein expression levels in gastric cancer, exploring associations with clinical outcomes. Analytical techniques encompassed volcano plots, protein-protein interaction networks, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Set Enrichment Analysis (GSEA), and immune infiltration assessments. Furthermore, lentiviral vectors containing interference sequences targeted at LBP were employed to manipulate its expression in AGS and HGC-27 gastric cancer cell lines, facilitating analyses of gene knockdown effects on cellular behaviors indicative of malignancy progression. Results: Our pan-cancer comparative analysis across 33 cancer types revealed a significant upregulation of LBP in gastric cancer, with diagnostic ROC curve analysis yielding an AUC of 0.765. Univariate and multivariate COX regression analyses identified high LBP expression as inversely related to patient survival. Additionally, immune infiltration and functional enrichment analyses indicated LBP's involvement in pathways crucial to cancer development, such as immune response modulation and lipid metabolism. Experimentally, LBP knockdown in gastric cancer cell lines resulted in reduced proliferation, migration, and invasion capabilities, underscoring its pivotal role in tumor dynamics. Conclusion: LBP is intricately linked to gastric cancer's pathogenesis, influencing cell proliferation, migration, and invasion, and thereby represents a valuable prognostic and diagnostic biomarker. This Study not only highlights LBP's potential as a therapeutic target but also lays the groundwork for future investigations into its mechanistic pathways in gastric cancer.