Construction of a nine DNA repair-related gene prognostic classifier to predict prognosis in patients with endometrial carcinoma

构建九个DNA修复相关基因预后分类器以预测子宫内膜癌患者的预后

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作者:Jinhui Liu, Pinping Jiang, Xucheng Chen, Yujie Shen, Guoliang Cui, Ziyan Ma, Shaojie Zhao, Yan Zhang

Background

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.

Conclusions

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.

Methods

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.

Results

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. Conclusions: 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.

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