[关键词]
[摘要]
目的:通过生物信息学方法分析与干眼(DE)发病机制相关的差异蛋白质,以期揭示其潜在的分子机制。
方法:通过检索从建库至2023-08-31发表在PubMed和EMBASE数据库中的采用蛋白质组学方法检测干眼临床样本中蛋白质表达的文章,挑选出差异蛋白,并通过STRING数据库和Cytoscape软件进行枢纽基因筛选和模块分析,进行蛋白质-蛋白质相互作用(PPI)分析、基因本体(GO)功能注释和京都基因与基因组百科全书(KEGG)通路富集分析。
结果:最终纳入21篇文献,确定74个差异表达的蛋白质。频率最高的差异蛋白为钙粒蛋白A(calgranulin A,SA1008)、脂质运载蛋白1(LCN1)、溶菌酶(LYZ)、乳腺珠蛋白-B(SCGB2A1)、富脯氨酸蛋白4(PRR4)、转铁蛋白(TF)和钙粒蛋白B(S100A9)。前10个枢纽基因为血清白蛋白(ALB)、肿瘤坏死因子(TNF)、白介素6(IL6)、IL1β、IL8、基质金属蛋白酶9(MMP9)、α-抗胰蛋白酶(SERPINA1)、IL10、补体C3(C3)和乳铁蛋白(LTF)。模块分析推测种子基因为MMP9和PRR4。KEGG分析显示差异表达的蛋白主要富集在IL17信号通路(61.9%)。
结论:研究结果揭示了DE的潜在分子靶点和途径,并证实了DE的发病机制与炎症之间的关联。然而,还需要进一步深入研究以证实这些生物标志物在临床实践中的意义。
[Key word]
[Abstract]
AIM:To analyze differential proteins associated with the pathogenesis of dry eye(DE)using bioinformatics methods, in order to reveal their potential molecular mechanisms.
METHODS: Articles published in PubMed and EMBASE databases from the inception of the database to August 31, 2023, that used proteomic methods to detect protein expression in clinical samples of dry eye were searched. Differential proteins were selected and further analyzed using the STRING database and Cytoscape software for hub gene screening and module analysis. Protein-protein interaction(PPI)analysis, gene ontology(GO)functional annotation, and Kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment analysis were performed.
RESULTS: A total of 21 articles were included, identifying 74 differentially expressed proteins. The most frequently occurring differential proteins were calgranulin A(SA1008), lipocalin-1(LCN1), lysozyme C(LYZ), mammaglobin-B(SCGB2A1), proline-rich protein 4(PRR4), transferrin(TF), and calgranulinB(S100A9). The top 10 hub genes were serum albumin(ALB), tumor necrosis factor(TNF), interleukin 6(IL6), IL1B, IL8, matrix metalloproteinase 9(MMP9), alpha-1-antitrypsin(SERPINA1), IL10, complement component 3(C3), and lactotransferrin(LTF). Module analysis suggested MMP9 and PRR4 as seed genes. KEGG analysis showed that differential proteins were mainly enriched in the IL17 signaling pathway(61.9%).
CONCLUSION: The results reveal potential molecular targets and pathways for DE and confirm the association between the pathogenesis of DE and inflammation. Further in-depth research is needed to confirm the significance of these biomarkers in clinical practice.
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[基金项目]
国家自然科学基金资助项目(No.81904302); 上海市自然科学基金项目(No.22ZR1458500,21ZR1460100); 上海市卫生健康委员会项目(No.20234Y0066); 上海市“科技创新行动计划”启明星项目(扬帆专项)(No.23YF1442000)