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范可尼贫血中关键铁死亡基因及其预测和诊断价值

Key Ferroptosis Genes and their Predictive and Diagnostic Value in Fanconi Anemia.

作者信息

Meng C, Huang L, Huang H, Zhao Z, Fu X, Yao H, Wu B

机构信息

Department of Hematology, Hainan General Hospital (Hainan Affiliated Hospital of Hainan Medical University), Hainan Province, P.R China.

出版信息

Physiol Res. 2025 Apr 30;74(2):275-285.

Abstract

Fanconi anemia (FA) and ferroptosis both affect tumor-related processes. However, few studies have reported on genetic associations between FA and ferroptosis. Our study evaluated the usefulness of genes related to ferroptosis in predicting and diagnosing FA. Transcriptome sequencing data were collected from 11 normal participants and 21 patients with FA. Differential gene analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Ontology (GO) analysis, gene correlation analysis, protein-protein interaction network analysis, qRT-PCR, and pan-cancer analysis were performed. The pan-cancer analysis was carried out based on data obtained from the GTEx and TCGA databases. Two hundred ninety-eight differentially expressed genes were detected based on the comparison of FA patients and normal participants, among which four critical non-FA genes, MAD2L1, ASPM, PCNA, and TOP2A, were identified. Among the ferroptosis-related genes, five genes, including CDKN1A, EMC2, FDFT1, HSPB1, and MT1G, were identified as being associated with FA, and the areas under the curve (AUC) of these five ferroptosis-related genes were 0.907, 0.640, 0.902, 0.840, and 0.929, respectively. The AUC for the diagnosis of FA reached 1.000 when the five ferroptosis-related genes were used in combination. In addition, the expressions of CDKN1A, EMC2, FDFT1, and HSPB1 were associated with the prognosis of multiple cancers (P<0.05). The five ferroptosis-related genes CDKN1A, EMC2, FDFT1, HSPB1, and MT1G exhibited excellent predictive effects for the diagnosis of FA.

摘要

范科尼贫血(FA)和铁死亡均影响肿瘤相关进程。然而,很少有研究报道FA与铁死亡之间的遗传关联。我们的研究评估了与铁死亡相关的基因在预测和诊断FA中的作用。收集了11名正常参与者和21例FA患者的转录组测序数据。进行了差异基因分析、京都基因与基因组百科全书(KEGG)分析、基因本体论(GO)分析、基因相关性分析、蛋白质-蛋白质相互作用网络分析、qRT-PCR和泛癌分析。泛癌分析基于从GTEx和TCGA数据库获得的数据进行。基于FA患者与正常参与者的比较,检测到298个差异表达基因,其中鉴定出4个关键的非FA基因,即MAD2L1、ASPM、PCNA和TOP2A。在与铁死亡相关的基因中,包括CDKN1A、EMC2、FDFT1、HSPB1和MT1G在内的5个基因被鉴定为与FA相关,这5个与铁死亡相关基因的曲线下面积(AUC)分别为0.907、0.640、0.902、0.840和0.929。当联合使用这5个与铁死亡相关的基因时,FA诊断的AUC达到1.000。此外,CDKN1A、EMC2、FDFT1和HSPB1的表达与多种癌症的预后相关(P<0.05)。5个与铁死亡相关的基因CDKN1A、EMC2、FDFT1、HSPB1和MT1G对FA的诊断具有优异的预测效果。

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