基于生物信息学筛选与分析胰腺癌的生物标志物半胱氨酸蛋白酶抑制剂S

Screening and analyzing biomarker cystatin S for pancreatic adenocarcinoma based on bioinformatics

目的:应用生物信息学方法分析筛选与胰腺癌(PAAD)发生发展相关的基因,探究半胱氨酸蛋白酶抑制剂S(CST4)在PAAD中的表达、预后价值及生物学功能。方法:选取GEO数据库胰腺癌芯片GSE15471和GSE16515为研究对象,并筛选出两个芯片数据集共同的差异表达基因(DEGs)作为关键基因。应用GEDS分析CST4 mRNA在TCGA和CCLE数据库的表达情况,并通过GEPIA2进一步分析CST4在消化系统肿瘤及正常组织中的差异表达。应用Kaplan-Meier Plotter分析CST4mRNA表达与TCGA数据库中PAAD患者五年总生存率及无复发生存率的关系。TIMER2数据库分析PAAD患者CST4 mRNA表达与多种免疫细胞浸润情况的相关性。通过STRING构建CST4蛋白互作网络并进行GO功能富集分析。结果:筛选两个GEO数据芯片的DEGs,韦恩图取交集后获得关键基因CST4。基于TCGA和GTEx数据库分析显示CST4在PAAD中的表达明显高于正常胰腺组织。CST4表达水平与患者的预后呈负相关,与肿瘤相关成纤维细胞、CD4^(+)T细胞、巨噬细胞、中性粒细胞免疫浸润情况呈正相关。PPI网络图显示CST1、CSTA、CSTB、CTSB、CTSL与CST4相互作用连接度较高,GO分析提示CST4基因的表达与细胞蛋白质分解代谢过程、内肽酶活性的调节、细胞凋亡通路等密切相关。结论:CST4在PAAD组织中表达升高且高表达组患者预后不良,CST4有望成为PAAD诊断及患者不良预后潜在的生物标志物。

Objective:To analyze and screen genes related to the occurrence and development of pancreatic adenocarcinoma(PAAD)based on bioinformatics methods,and to explore the expression,prognostic value and biological function of cystatin S(CST4)in PAAD.Methods:The pancreatic cancer chips GSE15471 and GSE16515 in GEO database were selected as the research objects,and the common differentially expressed genes(DEGs)of the two chip data sets were selected as the key genes.GEDS was used to analyze the expression of CST4 mRNA in TCGA and CCLE databases,and GEPIA2 was used to further analyze the differential expression of CST4 in tumors and normal tissues of digestive system.Kaplan-Meier Plotter was used to analyze the relationship between the expression of CST4 mRNA and 5-year overall survival rate and recurrence free survival rate of PAAD patients in TCGA database.TIMER2 database was used to analyze the correlation between CST4 mRNA expression and infiltration of various immune cells in PAAD patients.CST4 protein interaction network was constructed by STRING and GO function enrichment analysis were carried out.Results:The DEGs of two GEO data chips were screened,and the key gene CST4 was obtained after the intersection of Venn diagrams.Based on the TCGA and GTEx database analysis showed CST4 in PAAD expression was significantly higher than normal pancreatic tissue.The expression level of CST4 was negatively correlated with the prognosis of patients,and was positively correlated with the immune infiltration of cancer association fibroblasts,CD4^(+)T cells,macrophages and neutrophils.The PPI network plot showed that CST1,CSTA,CSTB,CTSB,CTSL had high interactive connectivity with CST4,and GO analysis suggested that CST4 gene expression was closely related to cellular protein catabolic processes,regulation of endopeptidase activity,apoptosis pathways,and so on.Conclusion:The expression of CST4 is increased in PAAD,and the prognosis of patients was poor in the high expression group.CST4is expected to become a potential biomarker for the diagnosis of PAAD and the poor prognosis of patients.