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一种用于预测卵巢癌预后的铁死亡相关基因的新型定义风险特征。

A Novel Defined Risk Signature of the Ferroptosis-Related Genes for Predicting the Prognosis of Ovarian Cancer.

作者信息

Ye Ying, Dai Qinjin, Li Shuhong, He Jie, Qi Hongbo

机构信息

The Department of Obstetrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.

State Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality, Chongqing Medical University, Chongqing, China.

出版信息

Front Mol Biosci. 2021 Apr 1;8:645845. doi: 10.3389/fmolb.2021.645845. eCollection 2021.

Abstract

Ferroptosis is an iron-dependent, regulated form of cell death, and the process is complex, consisting of a variety of metabolites and biological molecules. Ovarian cancer (OC) is a highly malignant gynecologic tumor with a poor survival rate. However, the predictive role of ferroptosis-related genes in ovarian cancer prognosis remains unknown. In this study, we demonstrated that the 57 ferroptosis-related genes were expressed differently between ovarian cancer and normal ovarian tissue, and based on these genes, all OC cases can be well divided into 2 subgroups by applying consensus clustering. We utilized the least absolute shrinkage and selection operator (LASSO) cox regression model to develop a multigene risk signature from the TCGA cohort and then validated it in an OC cohort from the GEO database. A 5-gene signature was built and reveals a favorable predictive efficacy in both TCGA and GEO cohort ( < 0.001 and = 0.03). The GO and KEGG analysis revealed that the differentially expressed genes (DEGs) between the low- and high-risk subgroup divided by our risk model were associated with tumor immunity, and lower immune status in the high-risk group was discovered. In conclusion, ferroptosis-related genes are vital factors predicting the prognosis of OC and could be a novel potential treatment target.

摘要

铁死亡是一种铁依赖性的、受调控的细胞死亡形式,其过程复杂,由多种代谢物和生物分子组成。卵巢癌(OC)是一种高度恶性的妇科肿瘤,生存率较低。然而,铁死亡相关基因在卵巢癌预后中的预测作用尚不清楚。在本研究中,我们证明了57个铁死亡相关基因在卵巢癌组织和正常卵巢组织中的表达存在差异,基于这些基因,通过一致性聚类可将所有OC病例很好地分为2个亚组。我们利用最小绝对收缩和选择算子(LASSO) Cox回归模型从TCGA队列中构建了一个多基因风险特征,然后在来自GEO数据库的OC队列中进行了验证。构建了一个5基因特征,在TCGA和GEO队列中均显示出良好的预测效能(<0.001和=0.03)。GO和KEGG分析显示,我们的风险模型划分的低风险和高风险亚组之间的差异表达基因(DEGs)与肿瘤免疫相关,并且发现高风险组的免疫状态较低。总之,铁死亡相关基因是预测OC预后的重要因素,可能是一种新的潜在治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9922/8047312/e05fe19f7f81/fmolb-08-645845-g0001.jpg

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