Identification of N6-methyladenosine-associated ferroptosis biomarkers in cervical cancer.

IF 2.5 3区生物学

Hereditas Pub Date : 2025-04-07 DOI:10.1186/s41065-025-00418-3

Jinzhe Liu, Buwei Han, Xijiao Hu, Mengke Yuan, Zhiwei Liu

{"title":"Identification of N6-methyladenosine-associated ferroptosis biomarkers in cervical cancer.","authors":"Jinzhe Liu, Buwei Han, Xijiao Hu, Mengke Yuan, Zhiwei Liu","doi":"10.1186/s41065-025-00418-3","DOIUrl":null,"url":null,"abstract":"Background: Cervical cancer (CC) stands as a major contributor to female mortality. The pathogenesis of CC is linked with various factors. Our research aimed to unravel the underlying mechanisms of ferroptosis and m6A RNA methylation in CC through bioinformatics analysis.Methods: Three CC datasets, including GSE9750, GSE63514, and TCGA-CESC, were incorporated. m6A-related genes were derived from published sources, while ferroptosis-related genes were obtained from the FerrDb database. Differential expression and correlation analyses were performed to identify differentially expressed m6A-related ferroptosis genes (DE-MRFGs) in CC. Subsequently, the biomarkers were further identified using machine learning techniques. Gene Set Enrichment Analysis (GSEA) and Kaplan-Meier (KM) survival analysis were also performed to comprehend these biomarkers. Furthermore, a competing endogenous RNAs (ceRNA) network involving biomarkers was established. Finally, biomarkers expression were verified by real-time quantitative polymerase chain reaction (RT-qPCR).Results: From the DE-MRFGs, six genes, including ALOX12, EZH2, CA9, CDCA3, CDC25A, HSPB1, were selected. A nomogram constructed based on these biomarkers exhibited potential clinical diagnostic value for CC, with good diagnostic accuracy confirmed through calibration curves. GSEA unveiled associations of these biomarkers with cell proliferation, spliceosome, and base excision repair. KM survival analysis demonstrated significant differences in survival outcomes between high and low expressions of HSPB1, EZH2, and CA9 samples. A ceRNA network was constructed involving three biomarkers, such as CDC25A, CDCA3, and EZH2, 29 miRNAs, and 25 lncRNAs. In RT-qPCR verification, the expression of ALOX12, EZH2 and CDC25A was significantly higher in CC samples, while HSPB1 expression was higher in control samples.Conclusion: Six genes, namely ALOX12, EZH2, CA9, CDCA3, CDC25A, and HSPB1, were identified as m6A-regulated ferroptosis biomarkers in CC. These findings offer valuable insights into disease pathogenesis and hold promise for advancing CC treatment and prognosis.","PeriodicalId":12862,"journal":{"name":"Hereditas","volume":"162 1","pages":"53"},"PeriodicalIF":2.5000,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11974235/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Hereditas","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1186/s41065-025-00418-3","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}

引用次数: 0

Abstract

Background: Cervical cancer (CC) stands as a major contributor to female mortality. The pathogenesis of CC is linked with various factors. Our research aimed to unravel the underlying mechanisms of ferroptosis and m6A RNA methylation in CC through bioinformatics analysis.

Methods: Three CC datasets, including GSE9750, GSE63514, and TCGA-CESC, were incorporated. m6A-related genes were derived from published sources, while ferroptosis-related genes were obtained from the FerrDb database. Differential expression and correlation analyses were performed to identify differentially expressed m6A-related ferroptosis genes (DE-MRFGs) in CC. Subsequently, the biomarkers were further identified using machine learning techniques. Gene Set Enrichment Analysis (GSEA) and Kaplan-Meier (KM) survival analysis were also performed to comprehend these biomarkers. Furthermore, a competing endogenous RNAs (ceRNA) network involving biomarkers was established. Finally, biomarkers expression were verified by real-time quantitative polymerase chain reaction (RT-qPCR).

Results: From the DE-MRFGs, six genes, including ALOX12, EZH2, CA9, CDCA3, CDC25A, HSPB1, were selected. A nomogram constructed based on these biomarkers exhibited potential clinical diagnostic value for CC, with good diagnostic accuracy confirmed through calibration curves. GSEA unveiled associations of these biomarkers with cell proliferation, spliceosome, and base excision repair. KM survival analysis demonstrated significant differences in survival outcomes between high and low expressions of HSPB1, EZH2, and CA9 samples. A ceRNA network was constructed involving three biomarkers, such as CDC25A, CDCA3, and EZH2, 29 miRNAs, and 25 lncRNAs. In RT-qPCR verification, the expression of ALOX12, EZH2 and CDC25A was significantly higher in CC samples, while HSPB1 expression was higher in control samples.

Conclusion: Six genes, namely ALOX12, EZH2, CA9, CDCA3, CDC25A, and HSPB1, were identified as m6A-regulated ferroptosis biomarkers in CC. These findings offer valuable insights into disease pathogenesis and hold promise for advancing CC treatment and prognosis.

查看原文本刊更多论文

宫颈癌中n6 -甲基腺苷相关铁下垂生物标志物的鉴定。

背景：宫颈癌（CC）是女性死亡的主要原因。CC的发病机制与多种因素有关。我们的研究旨在通过生物信息学分析揭示CC中铁下垂和m6A RNA甲基化的潜在机制。方法：纳入GSE9750、GSE63514和TCGA-CESC 3个CC数据集。m6a相关基因来源于已发表的文献，而铁中毒相关基因来源于FerrDb数据库。通过差异表达和相关性分析，鉴定CC中差异表达的m6a相关铁下垂基因（de - mrfg），随后使用机器学习技术进一步鉴定生物标志物。基因集富集分析（GSEA）和Kaplan-Meier生存分析（KM）也被用来理解这些生物标志物。此外，还建立了一个涉及生物标志物的竞争内源性rna （ceRNA）网络。最后，通过实时定量聚合酶链反应（RT-qPCR）验证生物标志物的表达。结果：从de - mrgs中筛选出ALOX12、EZH2、CA9、CDCA3、CDC25A、HSPB1等6个基因。基于这些生物标志物构建的形态图显示了潜在的CC临床诊断价值，通过校准曲线证实了良好的诊断准确性。GSEA揭示了这些生物标志物与细胞增殖、剪接体和碱基切除修复的关联。KM生存分析显示，HSPB1、EZH2和CA9高表达和低表达样本的生存结果存在显著差异。构建了包含CDC25A、CDCA3和EZH2等3种生物标志物、29种mirna和25种lncrna的ceRNA网络。RT-qPCR验证，CC样品中ALOX12、EZH2和CDC25A的表达量显著升高，而HSPB1的表达量在对照样品中较高。结论：m6a调控的6个基因ALOX12、EZH2、CA9、CDCA3、CDC25A和HSPB1是CC中铁凋亡的生物标志物，这些发现为了解CC的发病机制提供了有价值的见解，并有望改善CC的治疗和预后。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Hereditas Biochemistry, Genetics and Molecular Biology-Genetics

CiteScore

3.80

自引率

3.70%

发文量

期刊介绍： For almost a century, Hereditas has published original cutting-edge research and reviews. As the Official journal of the Mendelian Society of Lund, the journal welcomes research from across all areas of genetics and genomics. Topics of interest include human and medical genetics, animal and plant genetics, microbial genetics, agriculture and bioinformatics.