切换至 "中华医学电子期刊资源库"

中华产科急救电子杂志 ›› 2024, Vol. 13 ›› Issue (01) : 49 -54. doi: 10.3877/cma.j.issn.2095-3259.2024.01.009

实验研究

血清无细胞RNA铁死亡相关基因预测早发型子痫前期的初步研究
李剑琦1,()   
  1. 1. 510150 广州医科大学附属第三医院妇产科 广东省产科重大疾病重点实验室 广东省普通高校生殖与遗传重点实验室
  • 收稿日期:2023-05-09 出版日期:2024-02-18
  • 通信作者: 李剑琦
  • 基金资助:
    广州市卫健委科技项目(20231A011091)

Prediction of early preeclampsia with ferroptosis-related genes in plasma cell-free RNA

Jianqi Li1,()   

  1. 1. Department of Obstetrics and Gynecology, The Third Affiliated Hospital of Guangzhou Medical University, Key Laboratory of Major Obstetric Diseases of Guangdong Province, Key Laboratory of Reproduction and Genetics of Guangdong Higher Education Institutes, Guangzhou 510150, China
  • Received:2023-05-09 Published:2024-02-18
  • Corresponding author: Jianqi Li
引用本文:

李剑琦. 血清无细胞RNA铁死亡相关基因预测早发型子痫前期的初步研究[J/OL]. 中华产科急救电子杂志, 2024, 13(01): 49-54.

Jianqi Li. Prediction of early preeclampsia with ferroptosis-related genes in plasma cell-free RNA[J/OL]. Chinese Journal of Obstetric Emergency(Electronic Edition), 2024, 13(01): 49-54.

目的

鉴定早发型子痫前期中具有诊断意义的新型铁死亡相关基因。

方法

首先从FerrDb数据库中获取258个铁死亡相关基因,从基因表达综合数据库中获取早发型子痫前期患者的血清无细胞RNA基因表达谱和临床信息。此外,通过线性模型微阵列数据分析筛选出差异表达基因,结合韦恩图得到与铁死亡相关的基因表达谱。本研究对这些铁死亡相关基因进行了功能富集分析,进一步将获得的铁死亡相关基因采用LASSO方法构建早发型子痫前期相关特征的模型,确定一些在早发型子痫前期诊断中关键的铁死亡相关基因。

结果

首先,通过线性模型微阵列数据分析获得早发型子痫前期差异表达基因共4011个,其中上调基因2774个,下调基因1237个;其次,获得了37个与铁死亡相关的差异表达基因,涉及程序性细胞死亡、细胞凋亡、自噬、程序性死亡-配体1表达和铁死亡信号通路;再次,经过多变量生存分析,整合了胎龄、子痫前期状态和37个与铁死亡相关的差异表达基因,成功构建了LASSO诊断模型;最终发现了15个铁死亡相关基因(IFNG、AKR1C1、CAV1、SLC1A4、ENPP2、ACVR1B、ULK1、ZNF419、BID、XBP1、GPX4、MAPK14、WIPI1、DPP4、SLC7A5),成为诊断早发型子痫前期的关键基因;最后,成功构建了早发型子痫前期的15个铁死亡相关基因相关的蛋白质-蛋白质相互作用网络。

结论

血清无细胞RNA中的15个铁死亡相关基因与早发型子痫前期存在相关性,未来需要进一步验证其在早发型子痫前期诊断的价值。

Objective

To identify novel ferroptosis-associated genes with diagnostic significance in early-onset preeclampsia.

Methods

First, we obtained 258 ferroptosis-related genes from the FerrDb database, and the plasma cell-free RNA gene expression profiles and clinical information of patients with early preeclampsia from the GEO database. In addition, the differentially expressed genes were screened out by LIMMA analysis, combined with the Venn diagram to obtain the gene expression profile related to Ferroptosis. Then, we performed a functional enrichment analysis of these ferroptosis-related genes. Further use the obtained ferroptosis-related genes for LASSO to construct a model of early preeclampsia-related features, and determine some key ferroptosis-related genes in the diagnosis of early preeclampsia.

Results

First, 4011 differentially expressed genes in early preeclampsia were obtained by LIMMA analysis, of which 2774 genes were up-regulated and 1237 genes were down-regulated. Secondly, 37 differentially expressed genes related to ferroptosis were obtained, which were involved in programmed cell death, apoptosis, Autophagy, PD-L1 expression, and Ferroptosis signaling pathways. Third, after multivariate survival analysis, we integrated gestational age, preeclampsia status and 37 differentially expressed genes related to ferroptosis, and successfully constructed a LASSO diagnostic model. Finally, 15 ferroptosis-related genes (IFNG, AKR1C1, CAV1, SLC1A4, ENPP2, ACVR1B, ULK1, ZNF419, BID, XBP1, GPX4, MAPK14, WIPI1, DPP4, and SLC7A5) were discovered, which became the key genes for the diagnosis of early preeclampsia. Fourth, a protein-protein interaction network related to 15 ferroptosis-related genes was successfully constructed.

Conclusions

The 15 ferroptosis-related genes in plasma cell-free RNA have significant diagnostic value for early preeclampsia and are expected to be potential therapeutic targets for early preeclampsia.

图1 早发型子痫前期中差异表达基因的表达谱 A:子痫前期差异表达基因火山图,按1倍差异表达计算,显示上调基因2774个,下调基因1237个;B:子痫前期中差异表达基因的热图
图2 4011个差异表达基因及37个铁死亡相关基因的功能富集分析 A: 4011个差异表达基因的信号通路;B:韦恩图共获取到37个差异表达的铁死亡相关基因;C: 37个铁死亡相关基因的信号通路;D:37个铁死亡相关基因的GO功能注释
图3 Metascape和String的15个铁死亡相关基因的蛋白质-蛋白质相互作用网络 A:按集群ID着色,其中共享相同集群ID的节点通常彼此靠近;B:按p值着色,其中包含更多基因的术语往往具有更显著的p值;C,D:基因列表中确定的蛋白质-蛋白质相互作用网络和MCODE成分;E:涉及15个铁死亡相关基因的前11个簇及其代表性富集项
[1]
Rasmussen M, Reddy M, Nolan R, et al. RNA profiles reveal signatures of future health and disease in pregnancy[J]. Nature2022601(7893):422-427.
[2]
Lisonkova S, Joseph KS. Incidence of preeclampsia: risk factors and outcomes associated with early-versus late-onset disease[J]. Am J Obstet Gynecol2013209(6):544.e1-544.e12.
[3]
Walker CK, Krakowiak P, Baker A, et al. Preeclampsia, placental insufficiency, and autism spectrum disorder or developmental delay[J]. JAMA Pediatr2015169(2):154-162.
[4]
Alese MO, Moodley J, Naicker T. Preeclampsia and HELLP syndrome, the role of the liver[J]. J Matern Fetal Neonatal Med202134(1):117-123.
[5]
Chen Z, Gan J, Zhang M, et al. Ferroptosis and its emerging role in pre-eclampsia[J]. Antioxidants (Basel)202211(7):1-23.
[6]
Xie Y, Hou W, Song X, et al. Ferroptosis: process and function[J]. Cell Death Differ201623(3):369-379.
[7]
Beharier O, Kajiwara K, Sadovsky Y. Ferroptosis, trophoblast lipotoxic damage, and adverse pregnancy outcome[J]. Placenta2021108:32-38.
[8]
Liao T, Xu X, Ye X, et al. DJ-1 upregulates the Nrf2/GPX4 signal pathway to inhibit trophoblast ferroptosis in the pathogenesis of preeclampsia[J]. Sci Rep202212(1):1-16.
[9]
Ding Y, Yang X, Han X, et al. Ferroptosis-related gene expression in the pathogenesis of preeclampsia[J]. Front Genet202213:1-14.
[10]
Moufarrej MN, Vorperian SK, Wong RJ, et al. Early prediction of preeclampsia in pregnancy with cell-free RNA[J]. Nature2022602(7898):689-694.
[11]
Zhou Y, Zhou B, Pache L, et al. Metascape provides a biologist-oriented resource for the analysis of systems-level datasets[J]. Nat Commun201910(1):1-10.
[12]
王红艳,白桂芹. 子痫前期的分类[J/OL]. 中华产科急救电子杂志202110(4):197-200.
[13]
杜培丽,孙雯,苏春宏,等. 不同亚型子痫前期患者母儿结局分析[J/OL]. 中华产科急救电子杂志202211(1):33-37.
[14]
任丹玉,王永红. 凝血功能指标和血小板参数对子痫前期及其严重程度的辅助诊断价值研究[J]. 中国全科医学201922(22):2698-2704.
[15]
欧海蔚,尤共平,孙鸿彩,等. 早发型重度子痫前期血浆外泌体miRNAs表达谱分析[J]. 局解手术学杂志202332(4):293-296.
[16]
林岩. GPx4基因多态性与子痫前期遗传易感性的相关性研究[D]. 青岛:青岛大学,2017.
[17]
宋鹏书,张奕梅,彭振仁,等. 氧化应激因子和铁死亡标志物在子痫前期孕妇中的表达情况及其临床意义[J]. 广西医学202345(4):382-385,390.
[1] 洪玮, 叶细容, 刘枝红, 杨银凤, 吕志红. 超声影像组学联合临床病理特征预测乳腺癌新辅助化疗完全病理缓解的价值[J/OL]. 中华医学超声杂志(电子版), 2024, 21(06): 571-579.
[2] 周容, 张亚萍, 廖宇, 程晓萍, 管玉龙, 潘广玉, 闫杰, 王贤芝, 苟中山, 潘登科, 李巅远. 超声在基因编辑猪-猴异种并联式心脏移植术中的应用价值[J/OL]. 中华医学超声杂志(电子版), 2024, 21(06): 617-623.
[3] 刘伟, 牛云峰, 安杰. LINC01232 通过miR-516a-5p/BCL9 轴促进三阴性乳腺癌的恶性进展[J/OL]. 中华乳腺病杂志(电子版), 2024, 18(06): 330-338.
[4] 奚玲, 仝瀚文, 缪骥, 毛永欢, 沈晓菲, 杜峻峰, 刘晔. 基于肌少症构建的造口旁疝危险因素预测模型[J/OL]. 中华普外科手术学杂志(电子版), 2025, 19(01): 48-51.
[5] 屈勤芳, 束方莲. 盆腔器官脱垂患者盆底重建手术后压力性尿失禁发生的影响因素及列线图预测模型构建[J/OL]. 中华腔镜泌尿外科杂志(电子版), 2024, 18(06): 606-612.
[6] 刘文竹, 唐窈, 刘付臣. 诱导多潜能干细胞在神经肌肉疾病研究中的应用进展[J/OL]. 中华细胞与干细胞杂志(电子版), 2024, 14(06): 367-373.
[7] 公宇, 廖媛, 尚梅. 肝细胞癌TACE术后复发影响因素及预测模型建立[J/OL]. 中华肝脏外科手术学电子杂志, 2024, 13(06): 818-824.
[8] 王贝贝, 崔振义, 王静, 王晗妍, 吕红芝, 李秀婷. 老年股骨粗隆间骨折患者术后贫血预测模型的构建与验证[J/OL]. 中华老年骨科与康复电子杂志, 2024, 10(06): 355-362.
[9] 王国强, 张纲, 唐建坡, 张玉国, 杨永江. LINC00839 调节miR-17-5p/WEE1 轴对结直肠癌细胞增殖、凋亡和迁移的影响[J/OL]. 中华消化病与影像杂志(电子版), 2024, 14(06): 491-499.
[10] 孙晗, 于冰, 武侠, 周熙朗. 基于循环肿瘤DNA 甲基化的结直肠癌筛查预测模型的构建与验证[J/OL]. 中华消化病与影像杂志(电子版), 2024, 14(06): 500-506.
[11] 陈倩倩, 袁晨, 刘基, 尹婷婷. 多层螺旋CT 参数、癌胚抗原、错配修复基因及病理指标对结直肠癌预后的影响[J/OL]. 中华消化病与影像杂志(电子版), 2024, 14(06): 507-511.
[12] 丁富贵, 吴泽涛, 董卫国. 家族性腺瘤性息肉病临床特征及生物信息学分析[J/OL]. 中华消化病与影像杂志(电子版), 2024, 14(06): 512-518.
[13] 韦巧玲, 黄妍, 赵昌, 宋庆峰, 陈祖毅, 黄莹, 蒙嫦, 黄靖. 肝癌微波消融术后中重度疼痛风险预测列线图模型构建及验证[J/OL]. 中华临床医师杂志(电子版), 2024, 18(08): 715-721.
[14] 蔡晓雯, 李慧景, 丘婕, 杨翼帆, 吴素贤, 林玉彤, 何秋娜. 肝癌患者肝动脉化疗栓塞术后疼痛风险预测模型的构建及验证[J/OL]. 中华临床医师杂志(电子版), 2024, 18(08): 722-728.
[15] 王誉英, 刘世伟, 王睿, 曾娅玲, 涂禧慧, 张蒲蓉. 老年乳腺癌新辅助治疗病理完全缓解的预测因素分析[J/OL]. 中华临床医师杂志(电子版), 2024, 18(07): 641-646.
阅读次数
全文


摘要