整合与铁死亡有关的基因(FRGs)和预测模型以提高C型子宫内膜癌(UCEC)预后预测和治疗见解的准确性。
Integrating ferroptosis-related genes (FRGs) and prognostic models to enhance UCEC outcome prediction and therapeutic insights.
发表日期:2023 Aug 25
作者:
Weiwei Jin, Xiaoping Zhuang, Yihe Lin, Xiaoying Zhao
来源:
GENES & DEVELOPMENT
摘要:
铁死亡(Ferroptosis)与子宫体内膜癌(UCEC)的发展密切相关。本研究旨在发现新的潜在生物标志物,以预测UCEC的预后。在本研究中,从TCGA数据库中获取了包含382个FRGs的UCEC转录组数据和临床信息。我们进行了单变量Cox回归分析来评估与铁死亡相关基因(FRGs)的预后意义。然后,使用LASSO-Cox分析来构建一个预后模型。通过各种蛋白质组学分析和临床样本中的表达检测进一步表征了模型基因。构建了一个包含四个FRGs(CDKN1A、CDKN2A、CEBPG、NOS2)的多变量Cox回归模型。在四个FRGs中,CDKN2A、CEBPG和NOS2的高表达与较差的总生存概率相关,而CDKN1A的高表达与较好的总生存概率相关。风险模型的受试者工作特征曲线下面积分别为1年、3年和5年的时间点分别为0.617、0.688和0.693。此外,蛋白质组学分析显示,CDKN1A、CDKN2A和CEBPG的蛋白质表达在肿瘤组织中高于正常组织。CDKN1A和CDKN2A的高蛋白表达预示着较差的生存概率。此外,CDKN1A蛋白与CDKN2A蛋白或NOS2蛋白存在相互作用关系。在临床样本中,不论基因表达还是蛋白质表达,这四个FRGs在UCEC组织中均上调。我们的四个FRGs风险模型为预测UCEC患者的预后提供了新的见解。© 2023. 作者(在恩泽中)独家许可给波兰科学院植物遗传学研究所。
Ferroptosis is closely associated with uterine corpus endometrial carcinoma (UCEC) development. This project aimed to identify new potential biomarkers to predict the prognosis of UCEC. In this work, UCEC transcriptome data along with clinical information was retrieved from the TCGA database including a total of 382 FRGs. We performed univariate Cox regression analysis to evaluate ferroptosis-related genes (FRGs) for prognostic significance. The genes with prognostic significance were then analyzed using LASSO-Cox to construct a prognosis model. The model genes were further characterized through various proteomic analyses and expression detection in clinical samples. A multivariate Cox regression model was constructed containing four FRGs (CDKN1A, CDKN2A, CEBPG, NOS2). Among four FRGs, higher expressions of CDKN2A, CEBPG, and NOS2 were associated with poorer overall survival probability, while higher expression of CDKN1A was associated with better overall survival probability. The area under the receiver operating characteristic curve of the risk model was 0.617, 0.688, and 0.693 for 1 year, 3 years, and 5 years, respectively. Moreover, proteomic analysis showed that the protein expression of CDKN1A, CDKN2A, and CEBPG was higher in tumor tissues than that in normal tissues. Higher protein expression of CDKN1A and CDKN2A predicted poorer survival probability. Besides, CDKN1A protein had an interaction relationship with CDKN2A protein or NOS2 protein. In clinical samples, all four FRGs were upregulated in UCEC tissues, regardless of gene expression or protein expression. Our four FRGs risk model provides new insights for predicting the prognosis of UCEC patients.© 2023. The Author(s), under exclusive licence to Institute of Plant Genetics Polish Academy of Sciences.