基于生物信息学分析E74样转录因子3在卵巢浆液性囊腺癌中的表达及作用机制

Expression of ELF3 in ovarian serous cystadenocarcinoma and its value for diagnosis and prognosis-an analysis based on bioinformatics

目的采用生物信息学方法探讨E74样转录因子3(ELF3)mRNA在卵巢浆液性囊腺癌中的表达水平,及其对卵巢浆液性囊腺癌的诊断、预后评估价值,并分析其可能的作用机制。方法从癌症基因组图谱数据库(TCGA)中获取2006至2021年内收录的379例卵巢浆液性囊腺癌组织样本和88例正常卵巢组织样本的临床信息以及ELF3 mRNA表达数据分析其表达差异,获取基因表达综合数据库(GEO)GSE38666数据集中12例正常卵巢上皮细胞及18例卵巢浆液性囊腺癌上皮细胞的测序结果进行ELF3 mRNA表达水平验证。比较卵巢浆液性囊腺癌组织与正常卵巢组织、卵巢浆液性囊腺癌上皮细胞与正常卵巢上皮细胞ELF3表达情况;比较不同临床病理特征患者卵巢浆液性囊腺癌组织ELF3 mRNA表达水平;分析ELF3 mRNA表达水平对卵巢浆液性囊腺癌的诊断价值;比较ELF3 mRNA高表达与低表达患者预后;富集分析ELF3在卵巢浆液性囊腺癌中可能参与的信号通路。结果卵巢浆液性囊腺癌组织ELF3 mRNA表达水平高于正常卵巢组织(P<0.05)。卵巢浆液性囊腺癌上皮细胞ELF3 mRNA表达水平高于正常卵巢上皮细胞(P<0.05)。不同国际妇产科协会(FIGO)等级、初始治疗效果、种族、组织学分级、肿瘤发生部位、血管侵犯、肿瘤残留的患者卵巢浆液性囊腺癌组织ELF3 mRNA表达水平比较差异均无统计学意义(均P>0.05),年龄>60岁的患者卵巢浆液性囊腺癌组织ELF3 mRNA表达水平低于年龄≤60岁的患者(P<0.05)。ELF3 mRNA表达水平诊断卵巢浆液性囊腺癌的ROC曲线显示AUC为0.988,最佳截断值为4.450,灵敏度为0.988,特异度为0.977。ELF3 mRNA低表达患者总生存期和疾病特异性生存期均优于高表达患者(均P<0.05)。ELF3 mRNA表达相关的基因可能参与G蛋白偶联受体(GPCR)配体结合和神经元系统两条信号通路。结论ELF3 mRNA表达水平在卵巢浆液性囊腺癌中具有较高的诊断、预后评估价值,高表达患者预后较差,并可能通过GPCR配体结合和神经元系统两条信号通路发挥作用。

Objective To investigate the expression of E74-like transcription factor 3(ELF3)mRNA in ovarian serous cystadenocarcinoma(OV)and its diagnostic and prognostic value based on bioinformatics analysis.Methods The clinical and ELF3 mRNA expression data of 379 OV samples and 88 normal ovarian tissue samples were obtained from the TCGA database;and the sequencing results of 12 normal ovarian epithelial cells and 18 OV epithelial cells in GSE38666 data set of GEO database were used for verification.The expression levels of ELF3 between OV tissue and normal ovarian tissue,OV epithelial cells and normal ovarian epithelial cells were compared.The expression of ELF3 mRNA in OV tissue from patients with different clinicopathological features was compared.The diagnostic and prognostic values of ELF3 mRNA expression level in OV were analyzed.Enrichment score analysis was used for signaling pathways that ELF3 may be involved in OV.Results ELF3 mRNA was highly expressed in OV tissues compared to normal tissues(P<0.05)and in OV epithelial cells compared to normal ovarian epithelial cells(P<0.05).The expression levels of ELF3 mRNA were not related to FIGO grade,initial treatment effect,race,histological grade,tumor site,vascular invasion and tumor residual(all P>0.05).ELF3 mRNA ex-pression was higher in the younger age group(P<0.05).The area under the ROC curve(AUC)of ELF3 mRNA expression for diagnosing OV was 0.988,the optimal cutoff value was 4.450,the sensitivity was 0.988,and the specificity was 0.977.Pa-tients with high ELF3 expression had poor OS and DSS(all P<0.05).ELF3 might be involved in G protein coupled receptors(GPCR)ligand binding and neuronal system signaling pathways.Conclusion The expression level of ELF3 mRNA has high diagnostic and prognostic value in OV,and patients with high expression have poor prognosis.ELF3 may play a role through GPCR ligand binding and neuronal system signal pathways.