Department of Gynecology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
College of Pharmacy, Nanjing Medical University, Nanjing, China.
BMC Cancer. 2021 Jan 6;21(1):29. doi: 10.1186/s12885-020-07712-5.
Endometrial cancer (EC) is one of the most common gynecological malignancies worldwide. However, the molecular mechanisms and the prognostic prediction for EC patients remain unclear.
In the current study, we performed an in-depth analysis of over 500 patients which were obtained from the Cancer Genome Atlas (TCGA) database. The bioinformatics analysis included gene set enrichment analysis (GSEA) and Cox and lasso regression analyses to ensure overall survival (OS)-related genes, moreover, to construct a prognostic model and a nomogram for EC patients.
GSEA identified 4 gene sets significantly associated with EC, which are DNA repair, unfolded protein response, reactive oxygen species pathway and UV response up. Twenty-five OS-related DNA repair genes were screened out, after that, a 9-mRNA signature was constructed to measure the risk scores of patients with different outcomes. In addition, a nomogram contained the 9-mRNA model and clinical parameters was also presented to assess the prognosis. Patients with low risk were more likely to have sensitivity to paclitaxel, vinblastine, rapamycin, metformin, imatinib, Akt inhibitor and lapatinib.
The identified highly enriched gene sets may offer a novel insight into the tumorigenesis and treatment of EC. Additionally, the constructed 9-mRNA model and the nomogram have prominent clinical implications for prognosis evaluation and specific therapy guidance for EC patients.
子宫内膜癌(EC)是全球最常见的妇科恶性肿瘤之一。然而,EC 患者的分子机制和预后预测仍然不清楚。
在本研究中,我们对来自癌症基因组图谱(TCGA)数据库的 500 多名患者进行了深入分析。生物信息学分析包括基因集富集分析(GSEA)和 Cox 和套索回归分析,以确定与总体生存(OS)相关的基因,进而构建 EC 患者的预后模型和列线图。
GSEA 确定了与 EC 显著相关的 4 个基因集,分别是 DNA 修复、未折叠蛋白反应、活性氧途径和 UV 反应上调。筛选出 25 个与 OS 相关的 DNA 修复基因,然后构建了一个 9-mRNA signature,用于衡量不同结局患者的风险评分。此外,还提出了包含 9-mRNA 模型和临床参数的列线图,以评估预后。低风险患者对紫杉醇、长春碱、雷帕霉素、二甲双胍、伊马替尼、Akt 抑制剂和拉帕替尼更敏感。
鉴定出的高度富集基因集可能为 EC 的肿瘤发生和治疗提供新的见解。此外,构建的 9-mRNA 模型和列线图对 EC 患者的预后评估和特定治疗指导具有显著的临床意义。