| 宋 超,檀碧波,吴明利,等.层黏连蛋白β1在胃癌中表达的生物学意义及对患者预后的影响[J].肿瘤学杂志,2026,32(8):647-655. |
| 层黏连蛋白β1在胃癌中表达的生物学意义及对患者预后的影响 |
| Biological Significance of Laminin β1 Expression in Gastric Cancer and Its Prognostic Impact |
| 投稿时间：2026-04-02 |
| DOI：10.11735/j.issn.1671-170X.2026.08.B004 |
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| 中文关键词: 层黏连蛋白β1 胃肿瘤 上皮间质转化 列线图 预后 |
| 英文关键词:laminin β1 gastric neoplasms epithelial-mesenchymal transition Nomogram prognosis |
| 基金项目:河北省重点研发计划（22377701D） |
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| 摘要点击次数: 9 |
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| 中文摘要: |
| 摘 要：［目的］ 探讨层黏连蛋白β1（laminin β1，LAMB1）在胃癌进展中的作用及对患者预后的影响。［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年1月1日至12月31日于河北医科大学第四医院行外科手术的227例胃癌患者临床资料，按7∶3比例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］ 生物信息学分析显示，胃癌组织中LAMB1表达水平明显高于癌旁组织（P＜0.001），且其高表达与不良预后相关（P=0.042）；富集分析显示LAMB1与细胞黏附、EMT通路密切相关。qRT-PCR验证显示LAMB1在胃癌组织和胃癌细胞系中表达增高（t=39.02，P=0.007；F=6 172，P＜0.001）。慢病毒转染胃癌细胞后，LAMB1表达降低（F=1 947，P＜0.001），细胞的增殖能力降低（F=1 534，P＜0.001）；Western blot结果显示，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均＜0.001）；Transwell实验和划痕实验显示，LAMB1促进胃癌细胞的侵袭和迁移（F=128，P＜0.001；F=761，P＜0.001）。多因素Cox分析显示，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），且LAMB1高表达与胃癌患者不良预后显著相关（P＜0.001）。基于上述预后影响因素构建列线图模型，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年生存期曲线下面积分别为0.923和0.905，验证集3年和5年生存期曲线下面积分别为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。 |
| 英文摘要: |
| Abstract： ［Objective］ To investigate the role of laminin β1 (LAMB1) in the progression of gastric cancer and its impact on patient prognosis. ［Methods］ The Cancer Genome Atlas (TCGA) dataset and epithelial-mesenchymal transition (EMT)-related gene sets were downloaded to screen for differentially expressed EMT-associated genes in gastric cancer. Survival analysis， protein-protein interaction (PPI) network construction， and functional enrichment analysis were performed to explore the functions of differentially expressed genes. Quantitative real-time PCR (qRT-PCR)， CCK-8 assay， Western blot， Transwell assay， and wound healing assay were conducted to validate LAMB1 expression and its biological functions. Clinical data from 227 patients who underwent surgery at the Fourth Hospital of Hebei Medical University between January 1， 2019 and December 31， 2019 were retrospectively analyzed. Patients were randomly divided into a training set and a validation set at a 7∶3 ratio. A Cox regression-based clinical prediction model for postoperative prognosis was constructed. ［Results］ Bioinformatics analysis revealed that LAMB1 expression in gastric cancer tissues was significantly higher than that in adjacent normal tissues (P<0.001)， and its high expression was associated with poorly prognosis (P=0.042). Enrichment analysis showed that LAMB1 was closely related to cell adhesion and the EMT pathway. qRT-PCR validation confirmed increased LAMB1 expression in gastric cancer tissues and cell lines (t=39.02， P=0.007； F=6 172， P<0.001). After lentiviral-mediated knockdown of LAMB1 in gastric cancer cells， LAMB1 expression decreased (F=1 947， P<0.001)， and cell proliferation was reduced (F=1 534， P<0.001). Western blot analysis showed that LAMB1 knockdown increased E-cadherin expression， decreased N-cadherin and Vimentin expression(indicating a shift away from EMT)， upregulated the pro-apoptotic protein Bax， and downregulated the anti-apoptotic protein Bcl-2 (all P<0.001). Transwell and wound healing assays demonstrated that LAMB1 promoted the invasion and migration of gastric cancer cells (F=128， P<0.001； F=761， P<0.001). Multivariate Cox analysis identified age， alcohol consumption， lymphovascular invasion， neural invasion， pathological stage， and LAMB1 expression as independent prognostic factors for gastric cancer (P<0.05)， with high LAMB1 expression being significantly associated with poorly prognosis (P<0.001). A Nomogram model was constructed based on these factors. 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 area under the curve (AUC) for 3- and 5-year survival was 0.923 and 0.905 in the training set， and 0.923 and 0.899 in the validation set respectively， indicating good discriminative ability. Calibration curves and decision curve analysis confirmed satisfactory clinical utility of the model. ［Conclusion］ LAMB1 is highly expressed in gastric cancer and promotes proliferation， invasion， and migration by regulating the EMT pathway， which is closely associated with tumor progression and poorly prognosis of gastric cancer patients. |
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