GRB14基因在肺腺癌中的表达及对预后的影响

doi:10.20223/j.cnki.1000-8535.2025.11.003

广州医药 ›› 2025, Vol. 56 ›› Issue (11): 1482-1490.DOI: 10.20223/j.cnki.1000-8535.2025.11.003

GRB14基因在肺腺癌中的表达及对预后的影响

陈启宪¹, 何卫国¹, 何丽美¹, 梁志科², 徐豪明³, 郭明义⁴, 刘朝晖²

1 华南理工大学附属第二医院（广州市第一人民医院）南沙医院呼吸与危重症医学科（广东广州 511457）
2 华南理工大学附属第二医院（广州市第一人民医院）呼吸与危重症医学科（广东广州 510180）
3 华南理工大学附属第二医院（广州市第一人民医院）消化内科（广东广州 510180）
4 珠海市人民医院消化内科（广东珠海 519000）

收稿日期:2025-03-03 出版日期:2025-11-20 发布日期:2025-12-25
通讯作者: 刘朝晖,E-mail：gz_zhaohui_liu@sina.com
基金资助:
国家自然科学基金项目（82370552）

Expression and clinical significance of GRB14 in lung adenocarcinoma

CHEN Qixian¹, HE Weiguo¹, HE Limei¹, LIANG Zhike², XU Haoming³, GUO Mingyi⁴, LIU Zhaohui²

1 Pulmonary and Critical Care Medicine Department,Nansha Hospital,Guangzhou First People’s Hospital,the Second Affiliated Hospital,School of Medicine,South China University of Technology,Guangzhou 511457,China
2 Department of Pulmonary and Critical Care Medicine,Guangzhou First People’s Hospital,the Second Affiliated Hospital,School of Medicine,South China University of Technology,Guangzhou 510180,China
3 Department of Gastroenterology,Guangzhou First People’s Hospital,the Second Affiliated Hospital,School of Medicine,South China University of Technology,Guangzhou 510180,China
4 Department of Gastroenterology,Zhuhai People’s Hospital,Zhuhai 519000,China

Received:2025-03-03 Online:2025-11-20 Published:2025-12-25

摘要/Abstract

摘要： 目的初步探讨生长因子受体结合蛋白14（GRB14）在肺腺癌患者预后中的具体作用机制。方法通过TIMER 数据库、UALCAN数据库及GEPIA数据库,探讨GRB14 mRNA在肺腺癌及正常肺组织中的表达。运用免疫组织化学通过组织芯片（75例肺腺癌患者和75例癌旁组织）检测其蛋白表达水平,收集国外肿瘤研究团队上传至TCGA数据库229例肺腺癌患者的临床数据,分析评估GRB14在肺腺癌患者的表达及其临床特征及生存预后之间的关系。应用TIMER数据库对GRB14肺腺癌患者进行免疫浸润分析。String数据库探讨GRB14与其他蛋白之间是否存在相互作用。结果 TIMER数据库分析显示,相比正常组织,GRB14 mRNA在多种实体肿瘤和肺腺癌组织中高表达（P<0.05）。使用UALCAN数据库和GEPIA数据库以正常样本为对照组,肺腺癌患者的GRB14的表达均增加（P<0.01）。免疫组织化学检测组织芯片结果显示,GRB14蛋白在肺腺癌的表达高于正常肺组织（肺腺癌6.07±1.01 vs 癌旁组织4.80±1.22;P<0.01）。TCGA数据库分析显示,肺腺癌患者中GRB14高表达组和低表达组的中位总生存期分别为（41.59±5.20）月和（88.67±16.69）月;结合TCGA数据库绘制ROC曲线,发现GRB14的表达对肺腺癌患者具有一定的诊断价值。单因素回归分析结果显示,肿瘤分期（Ⅲ-Ⅳ）（P<0.01）、肿瘤原发灶的情况（T3-4）（P<0.01）、淋巴结转移（N1-3）（P<0.01）和GRB14表达（P<0.01）是影响肺腺癌中位总生存期的因素;Cox多因素回归分析显示,淋巴结转移（N1-3）（P<0.05）和GRB14表达（P<0.01）是影响肺腺癌中位总生存时间的因素。TIMER数据库分析显示,GRB14 mRNA 表达与巨噬细胞（r=-0.164,P<0.01）、中性粒细胞（r=-0.175,P<0.01）和树突状细胞（r=-0.148,P<0.01）具有相关性。通过String数据库分析发现与GRB14相互作用的蛋白质包括EGFR、HRAS、FGFR1、INSR、CNGA1、COBLL1、LYPLAL1、TNKS2、TNKS、PRKCZ。结论 GRB14表达增加与肺腺癌患者预后不良相关。

关键词: 生长因子受体结合蛋白14, 肺腺癌

Abstract: Objective To assess the specific mechanism of growth factor receptor-bound protein 14（GRB14）in the prognosis of lung adenocarcinoma（LUAD）patients．Methods The expression of GRB14 mRNA in LUAD and normal lung tissue was explored using TIMER database,UALCAN database,and GEPIA database．The expression of GRB14 protein was examined by immunohistochemistry using a tissue microarray．Then,the associations of GRB14 expression with clinicopathological features and clinical outcomes of LUAD were validated by analyzing TCGA database at the mRNA level and statistically evaluating the results．TIMER database was used to analyze immune infiltration of GRB14 in LUAD．Protein-protein interaction of GRB14 were analyzed using the String database．Results Using the TIMER database,we found that GRB14 mRNA was highly expressed in various solid tumors and LUAD tissues compared to normal tissues（P<0.05）．Comparing with the normal group,the expression of GRB14 was increased in LUAD（P<0.01）via using UALCAN database and GEPIA database．The expression level of GRB14 protein in the LUAD tissues was significantly higher than that in the noncancerous LUAD tissues（LUAD[6.07±1.01] vs benign,[4.80±1.22];P<0.01）in tissue microarray ．Median overall survival in the high and low GRB14 expression groups in LUAD was（41.59±5.2）and（88.67±16.69）months respectively．We plotted the ROC curves of 3-year survival rate and 5-year survival rate which again suggested that the model had good predictive performance．Univariate analysis revealed that individual cancer stages（Ⅲ-IV）（P<0.01）,tumor（T3-4）（P<0.01）,lymph node metastasis（N1-3）（P<0.05）and GRB14 expression（P<0.01）were risk factors affecting the median overall survival time of LUAD．According to Cox multiple regression analysis,we found that lymph node metastasis（N1-3）（P<0.05）and GRB14 expression（P<0.01）were risk factors affecting the median overall survival time of LUAD．Using TIMER database analysis,the mRNA level of GRB14 was significantly correlated with macrophages（r=-0.164,P<0.01）,neutrophils（r=-0.175,P<0.01）and dendritic cells（r=-0.148,P<0.01）．Through analysis of the String database,it was found that proteins that interacted with GRB14 including EGFR,HRAS,FGFR1,INSR,CNGA1,COBLL1,LYPLAL1,TNKS2,TNKS,PRKCZ．Conclusions The results of the present study suggest that GRB14 may efficiently predict poor survival in LUAD patients．

Key words: growth factor receptor-bound protein 14, lung adenocarcinoma

陈启宪, 何卫国, 何丽美, 梁志科, 徐豪明, 郭明义, 刘朝晖. GRB14基因在肺腺癌中的表达及对预后的影响[J]. 广州医药, 2025, 56(11): 1482-1490.

CHEN Qixian, HE Weiguo, HE Limei, LIANG Zhike, XU Haoming, GUO Mingyi, LIU Zhaohui. Expression and clinical significance of GRB14 in lung adenocarcinoma[J]. Guangzhou Medical Journal, 2025, 56(11): 1482-1490.

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GRB14基因在肺腺癌中的表达及对预后的影响

Expression and clinical significance of GRB14 in lung adenocarcinoma

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