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子宫内膜癌铁死亡相关预后模型的构建与验证

Construction and Validation of a Ferroptosis-Related Prognostic Model for Endometrial Cancer.

作者信息

Wang Hao, Wu Yingchen, Chen Shengfu, Hou Minzhi, Yang Yanning, Xie Meiqing

机构信息

Department of Gynecology and Obstetrics, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.

出版信息

Front Genet. 2021 Sep 28;12:729046. doi: 10.3389/fgene.2021.729046. eCollection 2021.

Abstract

Endometrial cancer (EC) is one of the most common female reproductive system tumors, with close to 200,000 new cases each year. It accounts for approximately 7% of the total number of female cancers, but until now the cause of EC has remained unclear. Ferroptosis is regulated cell death that distinguishes apoptosis and caused by oxidative damage. The process has unique biological effects on metabolism and redox biology. In this study, we analyzed the relationship between EC and ferroptosis. According to the different expression levels of related genes, we first divided 544 EC samples into four clusters and found that most of the infiltrating immune cells were significantly different among the four groups. A differential gene expression analysis between Fe.cluster groups was performed, and the samples were again divided into three Fe.gene.cluster groups. The molecular characteristics and clinical characteristics of the groups were significantly different. Finally, 13 characteristic genes were selected as ferroptosis gene signatures, and the Fe.score was obtained by calculation. The Fe.score is closely related to the clinical and molecular characteristics of EC, and a low Fe.score has a significant survival advantage. The GDSC predicts that the IC50 of multiple chemotherapeutic drugs is also significantly different between the two groups. In conclusion, our research has explored the relationship between EC and ferroptosis in detail, provides comprehensive insights for ferroptosis-mediated EC mechanism research, and emphasizes the clinical application potential of Fe.score-based immunotherapy strategies.

摘要

子宫内膜癌(EC)是最常见的女性生殖系统肿瘤之一,每年新增病例近20万例。它约占女性癌症总数的7%,但迄今为止,EC的病因仍不清楚。铁死亡是一种受调控的细胞死亡,有别于凋亡,由氧化损伤引起。该过程对代谢和氧化还原生物学具有独特的生物学效应。在本研究中,我们分析了EC与铁死亡之间的关系。根据相关基因的不同表达水平,我们首先将544份EC样本分为四个簇,发现四组中大多数浸润性免疫细胞存在显著差异。对铁簇组进行了差异基因表达分析,并将样本再次分为三个铁基因簇组。这些组的分子特征和临床特征存在显著差异。最后,选择13个特征基因作为铁死亡基因特征,并通过计算获得铁得分。铁得分与EC的临床和分子特征密切相关,低铁得分具有显著的生存优势。基因组药物敏感性预测数据库(GDSC)预测,两组之间多种化疗药物的半数抑制浓度(IC50)也存在显著差异。总之,我们的研究详细探讨了EC与铁死亡之间的关系,为铁死亡介导的EC机制研究提供了全面的见解,并强调了基于铁得分的免疫治疗策略的临床应用潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/85ec/8505971/7cf3d540a1dd/fgene-12-729046-g001.jpg

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