基于多数据库综合分析胰腺癌中TRIM29基因表达及甲基化水平的预后价值

Comprehensive Analysis of the Prognostic Value of TRIM29 Gene Expression and Methylation in Pancreatic Cancer Based on Multi-database

目的探究三结构域蛋白29(TRIM29)作为胰腺癌患者预后标志物的价值。方法通过生物信息学方法,利用TCGA、GEO、ICGC数据库探究TRIM29 mRNA表达及甲基化水平在胰腺癌患者预后中的作用。结果TRIM29在胰腺癌组织中显著上调(P<0.05)。TRIM29高表达的胰腺癌患者总生存期(OS)显著低于TRIM29低表达的胰腺癌患者(P<0.05)。Meta分析验证了TRIM29上调是胰腺癌患者OS的不利预后因素。TRIM29表达水平与胰腺癌T分期和病理分期密切相关(均P<0.05)。TRIM29表达水平是胰腺癌患者预后的独立危险因素(HR=1.19,95%CI=1.03~1.36,P<0.05)。列线图分析同样验证了TRIM29的预测能力。GO富集分析结果显示TRIM29可能具有调节细胞外基质结构成分,参与细胞间连接等分子功能;KEGG富集分析结果显示TRIM29可能与粘着斑和PI3K-Akt等信号通路相关。TRIM29甲基化水平和表达量呈负相关(r=-0.71,P<0.01),且TRIM29低甲基化的胰腺癌患者OS和无进展生存期(PFS)显著低于TRIM29高甲基化的胰腺癌患者(均P<0.05)。结论TRIM29在胰腺癌组织中呈现高表达和低甲基化水平,且与胰腺癌患者预后不良密切相关,甲基化调控可能在TRIM29促进胰腺癌的发生发展中具有重要作用。

Objective To explore the value of Tripartite Motif Containing 29(TRIM29)as a prognostic marker in patients with pancreatic cancer.Methods In this study,the role of TRIM29 mRNA expression and methylation levels in the prognosis of patients was investigated by bioinformatics methods with TCGA,GEO and ICGC databases.Results TRIM29 was significantly up-regulated in pancreatic cancer(P<0.05).Overall survival(OS)was significantly lower in pancreatic cancer patients with high expression of TRIM29 than in those with low expression of TRIM29(P<0.05).Meta-analysis confirmed that TRIM29 upregulation is an adverse prognostic factor for OS in patients with pancreatic cancer.The expression level of TRIM29 was closely correlated with T stage and pathological stage of pancreatic cancer(both P<0.05).TRIM29 expression level was an independent risk factor for prognosis of patients with pancreatic cancer(HR=1.19,95%CI=1.03-1.36,P<0.05).The prediction ability of TRIM29 was also verified by the nomogram analysis.GO enrichment analysis showed that TRIM29 may regulate the structural components of extracellular matrix and participate in molecular functions such as intercellular connectivity.KEGG enrichment analysis showed that TRIM29 may be related to adhesion spots and PI3K-Akt signaling pathways.The methylation level was negatively correlated with expression level of TRIM29(r=-0.71,P<0.01).The OS and progression-free survival(PFS)were significantly lower in pancreatic cancer patients with high methylation of TRIM29 than in those with low methylation of TRIM29(both P<0.05).Conclusion TRIM29 expression and hypomethylation levels are high in pancreatic cancer tissues,which is closely related to poor prognosis of pancreatic cancer patients.Methylation regulation may play an important role in the occurrence and development of pancreatic cancer promoted by TRIM29.