基于在线数据库分析E2F转录因子家族成员信使RNA在胰腺癌组织中表达水平及其在胰腺癌患者中的预后意义

Expression and prognostic value of E2F transcription factors mRNA in pancreatic cancer through analyzing the cancer genome atlas database

目的基于在线数据库分析阐明E2F转录因子家族成员mRNA在胰腺癌组织中的表达水平及其在胰腺癌患者中的预后意义。方法利用基因表达谱交互式分析(GEPIA)在线分析数据库,采用Mann-Whitney U检验及Kaplan-Meier生存分析的统计学方法分别分析E2F转录因子家族成员mRNA在179例胰腺癌与171例癌旁组织的差异性表达,分析其每百万转录本(TPM)表达差异,并分析E2F转录因子家族成员mRNA表达与胰腺癌病理分期之间的关系。基于Kaplan-Meier Plotter数据库分析E2F转录因子家族成员mRNA表达水平与胰腺癌患者预后的关系,及其在胰腺癌患者亚组中的预后价值。采用Mann-Whitney U检验比较胰腺癌与癌旁组织E2F转录因子家族成员的表达水平;并采用Log-rank检验及Kaplan-Meier法对数据库中的纳入患者进行预后分析。结果GEPIA数据库分析结果表明,胰腺癌组织中E2F转录因子家族成员mRNA表达均高于癌旁组织。其中,胰腺癌组织中E2F1、E2F3和E2F8 mRNA表达水平均显著高于癌旁组织,差异有统计学意义(P<0.01)。此外,TPM表达分析结果也提示胰腺癌组织中较高的E2F1、E2F3和E2F8 TPM水平,差异有统计学意义(P<0.05)。GEPIA数据库分析结果还提示E2F2、E2F3、E2F6以及E2F8 mRNA表达与胰腺癌患者肿瘤病理分期显著相关,差异有统计学意义(P<0.05)。Kaplan-Meier Plotter在线数据库分析结果提示,高表达的E2F1、E2F2、E2F3、E2F7以及E2F8 mRNA与胰腺癌患者较低的总体生存率显著相关(P<0.05),而高表达的E2F6则与胰腺癌患者较好的总体生存率显著相关(P<0.05)。此外,高表达的E2F1、E2F2、E2F3、E2F7以及E2F8 mRNA与胰腺癌患者较差的无复发生存率显著相关(P<0.05),而E2F4高表达则与胰腺癌患者无复发生存率较好显著相关(P<0.05)。亚组分析结果则表明E2F1、E2F2、E2F3、E2F7及E2F8在不同肿瘤阶段、不同性别以及不同突变负荷的胰腺癌患者中均具有一定的预后价值。结论E2F转录因子家族成员在胰腺癌中高表达且与胰腺癌患者预后较差显著相关,尤其在早期胰腺癌中,提示其可能成为早期胰腺癌预后预测及治疗的新靶点。

Objective To evaluate the expression and prognostic significance of E2F transcription factors mRNA in patients with pancreatic cancer based on online database.Methods The differential expression of E2F transcription factors mRNA and transcripts per million(TPM)between 179 pancreatic cancer tissues and 171 para-tumor tissues and the correlation between E2F transcription factors and different pathological stages of pancreatic cancer were evaluated using Gene Expression Profiling Interactive Analysis(GEPIA)online database using Mann-Whitney U test.Kaplan-Meier Plotter online database was used to explore the relationship between E2F transcription factors and prognosis of patients with pancreatic cancer and the prognostic value of E2F transcription factors in several pancreatic cancer patients′subgroups by the log-rank test and the Kaplan-Meier method.Results Higher E2F transcription factors mRNA expression was found in pancreatic cancer tissues than that in para-tumor tissues using GEPIA online database.Among them,E2F1,E2F3 and E2F8 mRNAs were significantly higher in pancreatic cancer tissues than those in para-tumor tissues(P<0.01).Moreover,this result was further confirmed by TPM analysis(P<0.05).In addition,the expression of E2F2,E2F3,E2F6 and E2F8 mRNA was significantly related to pathological stage of pancreatic cancer(P<0.05).Kaplan-Meier Plotter online database showed that higher E2F1,E2F2,E2F3,E2F7 and E2F8 mRNA expression levels were correlated with unfavorable overall survival(OS)(P<0.05),while higher E2F6 mRNA expression was correlated with a favorable OS(P<0.05).The higher E2F1,E2F2,E2F3,E2F7 and E2F8 mRNAs expression was also correlated with unfavorable recurrence free survival(RFS)(P<0.05),while higher E2F4 mRNA was correlated with a favorable RFS(P<0.05).Additionally,E2F1,E2F2,E2F3,E2F7 and E2F8 were further confirmed to be prognostic in some subgroups,such as different stages,genders and mutation burdens in pancreatic cancer patients.Conclusion Higher E2F transcription factors mRNA expression was detected in pancreatic cancer tissues than that in para-tumor tissues.Higher mRNAs expression of E2F1,E2F2,E2F3,E2F7 and E2F8 was significantly correlated with poorer prognosis of pancreatic cancer patients,especially in early stage.E2F transcription factors may be potential prognosis prediction and the therapeutic target in pancreatic cancer.