Department of Gynaecology and Obstetrics, Wenzhou Hospital of Integrated Traditional Chinese and Western Medicine, Wenzhou, 325000, China.
Department of Pathology, Wenzhou Hospital of Integrated Traditional Chinese and Western Medicine, Wenzhou, 325000, China.
J Appl Genet. 2023 Dec;64(4):723-735. doi: 10.1007/s13353-023-00779-3. Epub 2023 Aug 25.
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.
铁死亡与子宫内膜癌（UCEC）的发生发展密切相关。本项目旨在寻找新的潜在生物标志物，预测 UCEC 的预后。本研究从 TCGA 数据库中获取了 UCEC 转录组数据及临床信息，共包括 382 个 FRGs。我们进行单因素 Cox 回归分析评估铁死亡相关基因（FRGs）的预后意义。然后使用 LASSO-Cox 分析有预后意义的基因，构建预后模型。通过多种蛋白质组学分析和临床样本表达检测，进一步对模型基因进行特征分析。构建了包含 4 个 FRGs（CDKN1A、CDKN2A、CEBPG、NOS2）的多因素 Cox 回归模型。在 4 个 FRGs 中，CDKN2A、CEBPG 和 NOS2 的高表达与较差的总生存率相关，而 CDKN1A 的高表达与较好的总生存率相关。风险模型的 1 年、3 年和 5 年的 AUC 分别为 0.617、0.688 和 0.693。此外，蛋白质组学分析显示，肿瘤组织中 CDKN1A、CDKN2A 和 CEBPG 的蛋白表达高于正常组织。CDKN1A 和 CDKN2A 的高蛋白表达预示着更差的生存概率。此外，CDKN1A 蛋白与 CDKN2A 蛋白或 NOS2 蛋白具有相互作用关系。在临床样本中，无论基因表达还是蛋白表达，所有 4 个 FRGs 在 UCEC 组织中均上调。我们的 4 个 FRGs 风险模型为预测 UCEC 患者的预后提供了新的见解。
