研究动态
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宫颈癌患者铁死亡相关预后基因特征的鉴定和验证。

Identification and validation of ferroptosis-related prognostic gene signature in patients with cervical cancer.

发表日期:2024 Jul 31
作者: Xiao-Feng Ruan, Dan-Ting Wen, Zheng Xu, Ting-Ting Du, Zhao-Feng Fan, Fang-Fang Zhu, Jing Xiao
来源: Cell Death & Disease

摘要:

铁死亡是一种铁依赖性细胞死亡,与其他类型的受调节细胞死亡不同。大量研究表明铁死亡参与多种癌症的生物学过程。然而,铁死亡在宫颈癌(CC)中的作用仍不清楚。本研究旨在探讨铁死亡相关预后基因(FRPG)在CC中的表达谱及其预后价值。铁死亡相关基因(FRG)来自癌症基因组图谱(TCGA)和FerrDb数据库。核心 FRG 由相互作用基因检索搜索工具 (STRING) 网站确定。使用单变量和多变量 Cox 回归来识别 FRPG,并构建铁死亡相关的预后模型。 FRPGs 在临床标本中得到验证。通过 CIBERSORT 算法和 LM22 特征矩阵评估 FRPG 与肿瘤浸润免疫细胞之间的关系。利用注释、可视化和集成发现数据库(DAVID)探讨了FRPG的生物信息学功能。从数据库中筛选出33个显着上调的FRG和28个下调的FRG[P<0.05;错误发现率(FDR)<0.05;和 |log2 倍数变化 (FC)| ≥2]。发现 24 个基因彼此密切相互作用,被视为枢纽基因(程度≥3)。溶质载体家族 2 成员 1 (SLC2A1)、碳酸酐酶 IX (CA9) 和双氧化酶 1 (DUOX1) 被确定为 Cox 回归中总生存 (OS) 的独立预后特征。时间依赖性受试者工作特征 (ROC) 曲线显示了铁死亡相关预后模型的预测能力,尤其是 1 年 OS [曲线下面积 (AUC) =0.76]。与公开数据一致,我们的实验表明肿瘤组织中SLC2A1和DUOX1的mRNA水平以及SLC2A1、DUOX1和CA9的蛋白水平显着升高。进一步分析表明,根据我们的预后模型,低风险组和高风险组之间肿瘤浸润免疫细胞的比例存在显着差异。通过应用基因本体论(GO)富集和京都基因和基因组百科全书(KEGG)通路分析来探索FRPG的功能富集。在本研究中,描绘了CC中FRPG的特征。结果表明,针对铁死亡可能是 CC.2024 转化癌症研究的一种新的可靠生物标志物和替代疗法。版权所有。
Ferroptosis is an iron-dependent cell death, which is distinct from the other types of regulated cell death. Considerable studies have demonstrated that ferroptosis is involved in the biological process of various cancers. However, the role of ferroptosis in cervical cancer (CC) remains unclear. This study aims to explore the ferroptosis-related prognostic genes (FRPGs) expression profiles and their prognostic values in CC.The ferroptosis-related genes (FRGs) were obtained from The Cancer Genome Atlas (TCGA) and FerrDb databases. Core FRGs were determined by the Search Tool for the Retrieval of Interacting Genes (STRING) website. FRPGs were identified using univariate and multivariate Cox regressions, and the ferroptosis-related prognostic model was constructed. FRPGs were verified in clinical specimens. The relationship between FRPGs and tumor infiltrating immune cells were assessed through the CIBERSORT algorithm and the LM22 signature matrix. Bioinformatics functions of FRPGs were explored with the Database for Annotation, Visualization, and Integrated Discovery (DAVID).Thirty-three significantly up-regulated and 28 down-regulated FRGs were screened from databases [P<0.05; false discovery rate (FDR) <0.05; and |log2 fold change (FC)| ≥2]. Twenty-four genes were found closely interacting with each other and regarded as hub genes (degree ≥3). Solute carrier family 2 member 1 (SLC2A1), carbonic anhydrases IX (CA9), and dual oxidase 1 (DUOX1) were identified as independent prognostic signatures for overall survival (OS) in a Cox regression. Time-dependent receiver operating characteristic (ROC) curves showed the predictive ability of the ferroptosis-related prognostic model, especially for 1-year OS [area under the curve (AUC) =0.76]. Consistent with the public data, our experiments demonstrated that the mRNA levels of SLC2A1 and DUOX1, and the protein levels of SLC2A1, DUOX1, and CA9 were significantly higher in the tumor tissues. Further analysis showed that there was a significant difference in the proportion of tumor infiltrating immune cells between the low- and high-risk group based on our prognostic model. The function enrichment of FRPGs was explored by applying Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses.In this study, the features of FRPGs in CC were pictured. The results implicated that targeting ferroptosis may be a new reliable biomarker and an alternative therapy for CC.2024 Translational Cancer Research. All rights reserved.