Lv Hao, Lv Mei, Guo Xuyang, Zhu Xiaoman, Chao Yue, Li Dandan
Department of Gastroenterology Medicine (Endoscopy Center), China-Japan, Union Hospital of Jilin University, Changchun, Jilin, 130033, PR China.
Department of Gastroenterology, University of Health and Rehabilitation Sciences Affiliated, Qingdao Municipal Hospital Jiaozhou Road 1#, Qingdao, 266071, PR China.
BMC Gastroenterol. 2025 Mar 28;25(1):205. doi: 10.1186/s12876-025-03794-2.
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.
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.
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.
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.
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.
胃癌在全球范围内的发病率和死亡率呈上升趋势，由于缺乏有效的早期检测方法，面临着重大挑战，这导致干预措施的延迟，凸显了新型生物标志物的必要性。脂多糖结合蛋白（LBP）在肺癌、结肠癌和宫颈癌等癌症中发挥作用，已成为一个有前景的候选生物标志物。然而，其在胃癌中的具体作用和机制仍不清楚，需要进一步研究。
本研究利用来自癌症基因组图谱（TCGA）、基因表达综合数据库（GEO）和人类蛋白质图谱（HPA）的数据，评估胃癌患者中LBP的mRNA和蛋白质表达水平，并探讨它们与临床结局的关联。分析技术包括火山图、蛋白质-蛋白质相互作用网络、基因本体（GO）分析、京都基因与基因组百科全书（KEGG）分析、基因集富集分析（GSEA）和免疫浸润评估。此外，使用含有靶向LBP干扰序列的慢病毒载体来调控其在AGS和HGC-27胃癌细胞系中的表达，从而分析基因敲低对恶性行为的影响。进行蛋白质印迹法（WB）以验证LBP敲低对关键信号通路蛋白表达的影响。
我们对33种癌症类型的泛癌比较分析显示，胃癌中LBP显著上调，诊断性ROC曲线分析得出的AUC为0.765。单因素和多因素Cox回归分析显示，LBP高表达与患者生存率呈负相关。此外，免疫浸润和功能富集分析表明，LBP参与了对癌症发展至关重要的途径，如免疫反应调节和脂质代谢。胃癌细胞系中LBP敲低降低了细胞增殖、迁移和侵袭能力。WB证实LBP敲低后P65、P-P65、STAT3和P-STAT3的表达降低。
LBP与胃癌发病机制密切相关；它影响细胞增殖、迁移和侵袭，因此是一种有价值的预后和诊断生物标志物。本研究不仅突出了LBP作为治疗靶点的潜力，也为未来对其在胃癌中作用机制的研究奠定了基础。
不适用。我想说明的是，我们的研究不属于临床研究，因此不涉及与人类或动物受试者相关的伦理问题。本研究中使用的细胞是从一家认证的生物技术公司购买的已建立细胞系。所有实验程序均符合细胞系研究的标准研究方案和指南。
