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。
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．
炎症性肠病（IBD）作为一种慢性、易复发的炎症性疾病,被世界卫生组织归类为现代医疗领域的难治性疾病之一。其确切发病机制尚不清晰,目前主要认为与肠菌失衡触发宿主过度的肠黏膜免疫反应,进而在遗传易感性的个体中引发肠黏膜的损伤有关。目前,尚无特效的靶点能治愈IBD。过氧化物酶体增殖物激活受体（PPARs）作为核受体超家族的一员,在机体的生长发育、炎症调控以及代谢过程中扮演着重要角色,且被视为治疗包括IBD在内的多种疾病的重要潜在靶点,并被认为与肠道菌群关系密切。文章旨在探讨PPARs与肠道菌群的关系在IBD中的作用,从而挖掘IBD新的潜在诊疗靶点,开发新的治疗策略,为临床上IBD的诊断和治疗提供新的思路和方法。
Inflammatory bowel disease（IBD）,characterized as a chronic and recurrent inflammatory condition,is classified by the World Health Organization as one of the intractable diseases in modern medicine．The precise pathogenesis of IBD remains unclear,but current research widely believes that it is closely related to dysbiosis of the gut microbiota．Imbalance in the gut flora triggers an excessive immune response in the host’s intestinal mucosa,leading to mucosal damage in genetically susceptible individuals．To date,no specific targets have been identified that can cure IBD．Peroxisome proliferator-activated receptors（PPARs）,as members of the nuclear receptor superfamily,play significant roles in growth and development,inflammation regulation,and metabolic processes．They are regarded as potential effective targets for treating various diseases,including IBD,and are closely related to the gut microbiota．This review aims to discuss the progress in understanding the role of the relationship between PPARs and gut microbiota in IBD,so as to find new potential targets for the diagnosis and treatment of IBD,develop new treatment strategies,provide new ideas and methods for the diagnosis and treatment of IBD in clinical practice．
