Lipopolysaccharide-binding protein (LBP): a prognostic biomarker for gastric cancer linked to immune infiltration

Abstract

Background

Gastric cancer, characterized by rising global incidence and mortality, faces significant challenges due to the lack of effective early detection methods, delaying timely interventions and underscoring the need for novel biomarkers. Lipopolysaccharide-binding protein (LBP), implicated in cancers such as lung, colon, and cervical cancer, has emerged as a promising candidate. However, its specific roles and mechanisms in gastric cancer remain unclear, necessitating further investigation.

Methods

This study utilized data from The Cancer Genome Atlas (TCGA), the Gene Expression Omnibus (GEO), and the Human Protein Atlas (HPA) to assess LBP mRNA and protein expression levels in gastric cancer patients and explore their associations with clinical outcomes. Analytical techniques included volcano plots, protein-protein interaction networks, Gene Ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, gene set enrichment analysis (GSEA), and immune infiltration assessments. Furthermore, lentiviral vectors containing interference sequences targeting LBP were used to manipulate its expression in AGS and HGC-27 gastric cancer cell lines, enabling the analysis of gene knockdown effects on malignant behaviors. Western blotting (WB) was performed to validate the impact of LBP knockdown on the expression of key signaling pathway proteins.

Results

Our pan-cancer comparative analysis across 33 cancer types revealed significant upregulation of LBP in gastric cancer, with diagnostic ROC curve analysis yielding an AUC of 0.765. Univariate and multivariate Cox regression analyses revealed that high LBP expression was inversely related to patient survival. Additionally, immune infiltration and functional enrichment analyses revealed the involvement of LBP in pathways crucial to cancer development, such as immune response modulation and lipid metabolism. LBP knockdown in gastric cancer cell lines reduced proliferation, migration, and invasion. WB confirmed decreased expression of P65, P-P65, STAT3, and P-STAT3 upon LBP knockdown.

Conclusion

LBP is intricately linked to gastric cancer pathogenesis; it influences cell proliferation, migration, and invasion, thereby representing a valuable prognostic and diagnostic biomarker. This study not only highlights the potential of LBP as a therapeutic target but also provides the groundwork for future investigations into its mechanistic pathways in gastric cancer.

Clinical trial number

Not applicable. I would like to clarify that our research does not fall under clinical studies and therefore does not involve ethical concerns related to human or animal subjects. The cells used in this study are established cell lines purchased from a certified biotechnology company. All experimental procedures comply with standard research protocols and guidelines for cell line studies.