E2F2 诱导卵巢癌细胞中 MCM4、CCNE2 和 WHSC1 的上调，并预测总体生存率较差。

E2F2 induces MCM4, CCNE2 and WHSC1 upregulation in ovarian cancer and predicts poor overall survival.

机构信息

Department of Gynecology, the First Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.

出版信息

Eur Rev Med Pharmacol Sci. 2017 May;21(9):2150-2156.

Abstract

OBJECTIVE

To explore the genes co-upregulated with E2F2 in ovarian cancer and their association with survival outcomes in ovarian cancer patients.

MATERIALS AND METHODS

The raw data of GDS3592 was downloaded from GEO datasets for reanalysis. The overlapping subset between the top 150 upregulated genes in ovarian cancer epithelial cells (CEPIs) and the E2F2 positively correlated genes (Pearson's r≥0.5) in ovarian cancer cohort in TCGA was identified. The association between E2F2, MCM4, CCNE2 and WHSC1 and overall survival (OS) and recurrence-free survival (RFS) in ovarian cancer patients were assessed using Kaplan-Meier plotter.

RESULTS

E2F2 is a significantly upregulated transcription factor in CEPIs. MCM4, CCNE2, and WHSC1 are co-upregulated with E2F2 among the 308 ovarian cancer samples (Pearson's r=0.5159, 0.3963 and 0.4941 respectively). Enforced E2F2 expression significantly enhanced MCM4, CCNE2 and WHSC1 transcription in SKOV3 and A2780 cells. High E2F2 and CCNE2 expression are associated with worse OS (high E2F2, HR: 1.48, 95%CI: 1.17-1.85, p<0.01; high CCNE2, HR: 1.36, 95%CI: 1.15-1.6, p<0.01). High MCM expression might be associated with worse RFS at the margin of significance (HR: 1.18, 95%CI: 1.00-1.39, p=0.055).

CONCLUSIONS

MCM4, CCNE2, and WHSC1 are co-upregulated with E2F2 in ovarian cancer. Enforced E2F2 expression significantly increased MCM4, CCNE2, and WHSC1 expression in ovarian cancer cells. High E2F2 and CCNE2 expression are associated with worse OS among ovarian cancer patients.

摘要

目的

探讨与卵巢癌中 E2F2 共同上调的基因及其与卵巢癌患者生存结局的关系。

材料与方法

从 GEO 数据集下载 GDS3592 的原始数据进行重新分析。鉴定出卵巢癌细胞系（CEPIs）中前 150 个上调基因与 TCGA 卵巢癌队列中 E2F2 正相关基因（Pearson's r≥0.5）的重叠子集。使用 Kaplan-Meier 绘图仪评估 E2F2、MCM4、CCNE2 和 WHSC1 与卵巢癌患者总生存期（OS）和无复发生存期（RFS）的关系。

结果

E2F2 是 CEPIs 中显著上调的转录因子。在 308 例卵巢癌样本中，MCM4、CCNE2 和 WHSC1 与 E2F2 共同上调（Pearson's r 分别为 0.5159、0.3963 和 0.4941）。E2F2 表达的强制增强显著增强了 SKOV3 和 A2780 细胞中 MCM4、CCNE2 和 WHSC1 的转录。高 E2F2 和 CCNE2 表达与较差的 OS 相关（高 E2F2，HR：1.48，95%CI：1.17-1.85，p<0.01；高 CCNE2，HR：1.36，95%CI：1.15-1.6，p<0.01）。MCM 高表达可能与 RFS 接近显著相关（HR：1.18，95%CI：1.00-1.39，p=0.055）。