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| 层粘连蛋白β1在胃癌中表达的生物学意义及对患者预后的影响 |
| The biological significance of Laminin β1 expression in gastric cancer and its impact on patient prognosis |
| 投稿时间：2026-04-02 修订日期：2026-05-18 |
| DOI： |
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| 中文关键词: 层粘连蛋白β1 胃癌 上皮间质转化 列线图模型 |
| 英文关键词:Laminin β1 gastric cancer epithelial-mesenchymal transition nomogram |
| 基金项目:河北省省级科技计划资助（22377701D） |
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| 摘要点击次数: 11 |
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| 中文摘要: |
| 目的：细胞外基质（extracellular matrix, ECM）的改变是胃癌进展的重要因素，但其确切的潜在机制尚不明确。本研究旨在探讨层粘连蛋白β1（Laminin β1，LAMB1）在胃癌进展中的作用及作为新标志物的可行性。
方法：下载癌症基因组图谱（the cancer genome atlas, TCGA）数据集和上皮间质转化（epithelial-mesenchymal transition, EMT）数据集，筛选出差异表达的胃癌EMT相关基因。生存分析、蛋白质互作网络和富集分析探究差异基因功能，实时荧光定量PCR(quantitative real-time PCR, qRT-PCR)、CCK-8实验、Western Blot、transwell实验和划痕实验验证LAMB1表达及生物学功能。回顾性分析2019.01.01-2019.12.31于河北医科大学第四医院行外科手术的227例患者临床资料，按7：3随机分为训练集和验证集，COX回归构建胃癌术后预后临床预测模型。
结果：生物信息学分析发现，胃癌组织中LAMB1表达水平明显高于癌旁组织（P＜0.0001），且与不良预后相关（P=0.042），富集分析发现LAMB1与细胞粘附、EMT通路密切相关。通过qRT-PCR进行验证，LAMB1在胃癌组织和胃癌细胞系中表达增高（t=39.02,P=0.007；F=6172, P＜0.0001）。慢病毒转染胃癌细胞后，LAMB1表达降低（F=1947, P＜0.0001），细胞的增殖能力降低（F=1534, P＜0.0001），Western blot结果发现敲低LAMB1后，E-cadherin表达增加，N-cadherin和Vimentin表达减少，细胞倾向于非EMT；同时促凋亡蛋白Bax表达增加，抗凋亡蛋白Bcl-2表达减少，细胞凋亡增加（P＜0.0001）；同时，Transwell实验和划痕实验发现LAMB1促进胃癌细胞的侵袭和迁移（F=128, P＜0.0001；F=761, P＜0.0001）。通过单因素和多因素COX分析发现，年龄、饮酒、淋巴血管侵犯、神经侵犯、病理分期和LAMB1表达是胃癌患者预后的独立预测因素（P＜0.05），KM生存曲线发现LAMB1高表达与胃癌患者不良预后显著相关（P＜0.0001），训练集和验证集的一致性指数分别为0.852（95%CI: 0.809-0.893）和0.807（95%CI: 0.720-0.894），训练集3年和5年AUC分别为0.923和0.905，验证集3年和5年AUC分别为0.923和0.899，提示模型具有良好的区分能力；校准曲线和临床决策曲线显示模型具有良好的临床效能。
结论：LAMB1在胃癌高表达，调控EMT通路促进胃癌增殖、侵袭和迁移，与胃癌进展和不良预后密切相关，有望成为新肿瘤标志物。 |
| 英文摘要: |
| Background: Changes in the extracellular matrix (ECM) are important factors in the progression of gastric cancer, but the exact underlying mechanisms remain unclear. This study aims to explore the role of Laminin β1 (LAMB1) in the progression of gastric cancer and its feasibility as a novel biomarker.
Methods: The cancer genome atlas (TCGA) dataset and epithelial-mesenchymal transition (EMT) dataset were downloaded to screen for differentially expressed gastric cancer EMT-related genes. Survival analysis, protein-protein interaction network, and enrichment analysis were conducted to investigate the functions of differentially expressed genes. Quantitative real-time PCR (qRT-PCR), CCK-8 assay, Western Blot, transwell assay, and wound healing assay were performed to validate LAMB1 expression and biological functions. A retrospective analysis of clinical data from 227 patients who underwent surgical procedures at the Fourth Hospital of Hebei Medical University from January 1, 2019, to December 31, 2019, was conducted. The patients were randomly divided into a training set and a validation set in a 7:3 ratio. Cox regression was used to construct a clinical prediction model for postoperative prognosis of gastric cancer.
Results: Bioinformatics analysis revealed that the expression level of LAMB1 in gastric cancer tissues was significantly higher than that in adjacent normal tissues (P<0.0001) and was associated with poor prognosis(P=0.042). Enrichment analysis found that LAMB1 was closely related to cell adhesion and the EMT pathway. Validation by qRT-PCR showed increased expression of LAMB1 in gastric cancer tissues and cell line(t=39.02, P=0.007; F=6172, P<0.0001). After lentiviral transfection of gastric cancer cells, LAMB1 expression decreased( F=1947,P<0.0001), and cell proliferation was reduced( F=1534, P<0.0001). Western blot results indicated that knockdown of LAMB1 led to increased expression of E-cadherin, decreased expression of N-cadherin and Vimentin, and a tendency toward non-EMT; meanwhile, the expression of the pro-apoptotic protein Bax increased, while the anti-apoptotic protein Bcl-2 decreased, resulting in increased apoptosis (P<0.0001). Furthermore, Transwell and wound healing assays demonstrated that LAMB1 promoted the invasion and migration of gastric cancer cells( F=128,P<0.0001;F=761,P<0.0001). Univariate and multivariate COX analyses identified age, alcohol, lymphovascular invasion, perineural invasion, stage, and LAMB1 as independent predictors of prognosis in gastric cancer patients (P<0.05). KM survival curves showed that high LAMB1 expression was significantly associated with poor prognosis in gastric cancer patients (P<0.0001). The concordance indices for the training and validation sets were 0.852（95%CI: 0.809-0.893）and 0.807（95%CI: 0.720-0.894）, respectively. The 3-year and 5-year AUC values for the training set were 0.923 and 0.905, and for the validation set were 0.923 and 0.899, indicating good discriminative ability of the model. Calibration curves and clinical decision curves demonstrated good clinical performance of the model.
Conclusion: LAMB1 is highly expressed in gastric cancer, regulating the EMT pathway to promote gastric cancer proliferation, invasion, and migration, closely related to gastric cancer progression and poor prognosis, and is expected to become a new tumor marker. |
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