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), impli...

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Main Authors: Hao Lv, Mei Lv, Xuyang Guo, Xiaoman Zhu, Yue Chao, Dandan Li
Format: Article
Language:English
Published: BMC 2025-03-01
Series:BMC Gastroenterology
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Online Access:https://doi.org/10.1186/s12876-025-03794-2
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author Hao Lv
Mei Lv
Xuyang Guo
Xiaoman Zhu
Yue Chao
Dandan Li
author_facet Hao Lv
Mei Lv
Xuyang Guo
Xiaoman Zhu
Yue Chao
Dandan Li
author_sort Hao Lv
collection DOAJ
description 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.
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publishDate 2025-03-01
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spelling doaj-art-4d41b7d821454bc4a74cde328cbb3b892025-08-20T03:40:47ZengBMCBMC Gastroenterology1471-230X2025-03-0125112310.1186/s12876-025-03794-2Lipopolysaccharide-binding protein (LBP): a prognostic biomarker for gastric cancer linked to immune infiltrationHao Lv0Mei Lv1Xuyang Guo2Xiaoman Zhu3Yue Chao4Dandan Li5Department of Gastroenterology Medicine (Endoscopy Center), China-Japan, Union Hospital of Jilin UniversityDepartment of Gastroenterology, University of Health and Rehabilitation Sciences AffiliatedDepartment of Gastroenterology Medicine (Endoscopy Center), China-Japan, Union Hospital of Jilin UniversityDepartment of Gastroenterology Medicine (Endoscopy Center), China-Japan, Union Hospital of Jilin UniversityDepartment of Gastroenterology Medicine (Endoscopy Center), China-Japan, Union Hospital of Jilin UniversityDepartment of Gastroenterology Medicine (Endoscopy Center), China-Japan, Union Hospital of Jilin UniversityAbstract 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.https://doi.org/10.1186/s12876-025-03794-2Gastric cancerLipopolysaccharide-binding proteinBioinformatics analysisBiomarker
spellingShingle Hao Lv
Mei Lv
Xuyang Guo
Xiaoman Zhu
Yue Chao
Dandan Li
Lipopolysaccharide-binding protein (LBP): a prognostic biomarker for gastric cancer linked to immune infiltration
BMC Gastroenterology
Gastric cancer
Lipopolysaccharide-binding protein
Bioinformatics analysis
Biomarker
title Lipopolysaccharide-binding protein (LBP): a prognostic biomarker for gastric cancer linked to immune infiltration
title_full Lipopolysaccharide-binding protein (LBP): a prognostic biomarker for gastric cancer linked to immune infiltration
title_fullStr Lipopolysaccharide-binding protein (LBP): a prognostic biomarker for gastric cancer linked to immune infiltration
title_full_unstemmed Lipopolysaccharide-binding protein (LBP): a prognostic biomarker for gastric cancer linked to immune infiltration
title_short Lipopolysaccharide-binding protein (LBP): a prognostic biomarker for gastric cancer linked to immune infiltration
title_sort lipopolysaccharide binding protein lbp a prognostic biomarker for gastric cancer linked to immune infiltration
topic Gastric cancer
Lipopolysaccharide-binding protein
Bioinformatics analysis
Biomarker
url https://doi.org/10.1186/s12876-025-03794-2
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