| Objective:Serpin Family EMember 1(SERPINE1)is a gene encoding a member of the serine protease inhibitor family.It has been reported to be overexpressed in a variety of malignancies such as breast,colorectal,bladder and lung cancers and is regarded as a biomarker of poor prognosis.The purpose of this study was to investigate the relationship between SERPINE1 expression and the prognosis of gastric cancer(GC)by bioinformatics and to study the possible related mechanisms.Methods:The m RNA expression data and clinical data information of gastric cancer patients were downloaded in The Cancer Genome Atlas(TCGA)database.Differential expression analysis,survival analysis and construction of receiver operating curves were performed using R language,and data validation was performed using the Gene Expression Profiling Interactive Analysis(GEPIA)database.Univariate Cox regression analysis and multivariate Cox regression analysis were used to determine independent prognostic factors in patients with gastric cancer.SERPINE1-related signaling pathways in gastric cancer were identified by Gene Set Enrichment Analysis(GSEA)software.The association between SERPINE1 methylation levels and the prognosis of gastric cancer patients was analyzed using Meth Surv database,Survival Meth database and UALCAN database.The association between SERPINE1 and different cancer immune cells was analyzed using the TIMER database.Finally,drug sensitivity analysis was performed using the Cell Miner database.Results: The results of differential expression analysis showed that the expression of SERPINE1 in gastric cancer tissues was higher than that in normal gastric tissues,p < 0.05;the results of survival analysis showed that the survival time of the high SERPINE1 expression group was lower than that of the low SERPINE1 expression group,p < 0.05;GEPIA databases verified this result.Univariate Cox regression analysis and multivariate Cox regression analysis showed that SERPINE1 expression was an independent prognostic factor in gastric cancer patients,p < 0.05.The time-dependent areaunder the receiver operating characteristic curve(AUC)at 1,3,and 5 years was 0.612,0.664,and0.753,respectively,confirming the high accuracy of SERPINE1 for predicting the prognosis of gastric cancer patients.GSEA analysis showed that there were 5 down-regulated pathways and 48 upregulated pathways of SERPINE1 gene,involving DNA replication pathway and mammalian target of rapamycin(m TOR)signaling pathway,toll-like receptors(TLR)signaling pathway,natural killer cell(NK)-mediated cytotoxicity pathway and other immune pathways.SERPINE1 methylation mainly involved 14 Cp G sites,of which cg25826546 was significantly correlated with overall survival(OS),and the survival time of the lower group was significantly higher,p < 0.05.When high SERPINE1 expression was analyzed using the TIMER database,CD8 + T cells,neutrophils,macrophages,and dendritic cells showed high immune infiltration levels,and immune checkpoint cytotoxic T-lymphocyte-associated protein 4(CTLA4),cluster of differentiation 274(CD274),and programmed cell death protein 1(PDCD1)showed high expression status,and SERPINE1 copy number changes could significantly affect the infiltration level of immune cells in gastric cancer.Drug sensitivity analysis using the Cell Miner database suggested that high SERPINE1 expression resulted in reduced drug sensitivity for Tegafur,Fluorouracil,and Paclitaxel,but increased sensitivity for Everolimus.Conclusions:In this study,the following conclusions can be drawn: 1.High expression of SERPINE1 predicts poor prognosis in patients with gastric cancer and is an independent prognostic factor;2.The relevant signaling pathways of SERPINE1 in gastric cancer mainly include tyrosine kinase-signal transducer and activator of transcription(JAK-STAT)signaling pathway,transforming growth factor-β(TGF-β)signaling pathway,m TOR signaling pathway,toll-like receptor signaling pathway,natural killer cell-mediated cytotoxicity,DNA replication,cancer pathway and vascular endothelial growth factor(VEGF)signaling pathway.3.The mechanism by which high SERPINE1 expression leads to poor prognosis in gastric cancer patients is related to DNA methylation,immune cell infiltration and tumor cell resistance. |
