[1]宋 园,屈小红,李维玲,等.胎膜早破并发绒毛膜羊膜炎患者胎盘组织中组蛋白H3K4me3，H3K27me3及修饰酶表达的临床价值研究[J].现代检验医学杂志,2025,40(02):174-179.[doi:10.3969/j.issn.1671-7414.2025.02.033]
　SONG Yuan,QU Xiaohong,LI Weiling,et al.Clinical Value of Histone H3K4me3, H3K27me3 and Modifying Enzyme Expression in Placental Tissue of Patients with Premature Rupture of Fetal Membrane Complicated with Chorioamnionitis[J].Journal of Modern Laboratory Medicine,2025,40(02):174-179.[doi:10.3969/j.issn.1671-7414.2025.02.033]
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胎膜早破并发绒毛膜羊膜炎患者胎盘组织中组蛋白H3K4me3，H3K27me3及修饰酶表达的临床价值研究()
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《现代检验医学杂志》[ISSN:/CN:]

卷:
第40卷
期数:
2025年02期
页码:
174-179
栏目:
论著
出版日期:
2025-03-15

文章信息/Info

Title:
Clinical Value of Histone H3K4me3, H3K27me3 and Modifying Enzyme Expression in Placental Tissue of Patients with Premature Rupture of Fetal Membrane Complicated with Chorioamnionitis
文章编号:
1671-7414（2025）02-174-06
作者:
宋 园1; 屈小红2; 李维玲1; 李花繁1; 刘 云1
（1. 西安高新医院妇产科，西安 710060；2. 西安国际医学中心医院产科，西安 710100）
Author(s):
SONG Yuan1; QU Xiaohong2; LI Weiling1; LI Huafan1; LIU Yun1
(1. Department of Obstetrics and Gynecology， Xi’an Gaoxin Hospital，Xi’an 710060，China；2. Department of Obstetrics，Xi’an International Medical Center Hospital，Xi’an 710100，China)
关键词:
胎膜早破; 组织学绒毛膜羊膜炎; 组蛋白修饰; 组蛋白H3 第4 位赖氨酸三甲基化; 组蛋白H3 第27 位赖氨酸三甲基化
分类号:
R714.433；R446
DOI:
10.3969/j.issn.1671-7414.2025.02.033
文献标志码:
A
摘要:
目的 研究分析胎膜早破（PROM）并发绒毛膜羊膜炎患者胎盘组织中组蛋白H3第4位赖氨酸三甲基化（H3K4me3）、组蛋白H3 第27 位赖氨酸三甲基化（H3K27me3）及修饰酶的表达水平及其临床意义。方法 回顾性收集2021 年6 月～ 2023年12 月因PROM 在西安高新医院就诊的95 例孕妇临床资料，根据是否并发组织学绒毛膜羊膜炎（HCA）分为感染组（n=41）和非感染组（n=54）；另选取同期30 例正常妊娠产妇作为对照组。取所有受试者胎盘组织，检测H3K4me3，H3K27me3 的表达水平；实时荧光定量PCR（qRT-PCR）检测H3K4me3，H3K27me3 特异性甲基化转移酶[ 混合谱系白血病蛋白1(MLL1)，Zeste 增强子同源物2（EZH2）] 和去甲基化转移酶[ 赖氨酸特异性去甲基化酶5B（KDM5B），Jumonji结构域包含蛋白3（JMJD3）] 水平。分析三组H3K4me3，H3K27me3 及特异性修饰酶表达差异及与HCA 组织学分期的相关性；绘制受试者工作特征（ROC）曲线，计算曲线下面积（AUC）值，评估H3K4me3，H3K27me3 对并发 HCA 感染的预测价值。结果 与对照组相比，感染组和非感染组H3K4me3（0.08%±0.02%，0.12%±0.03% vs 0.25%±0.06%）及MLL1 mRNA（1.32±0.16，1.44±0.23 vs 2.02±0.31），JMJD3 mRNA（0.78±0.13， 0.91±0.15 vs 1.53±0.23）水平明显降低（t=10.939～19.062），H3K27me39（0.23%±0.05%，0.15%±0.03% vs 0.10%±0.02%）及EZH2 mRNA（1.96±0.26，1.85±0.25vs 1.15±0.29），KDM5B mRNA（1.46±0.15，1.35±0.18 vs 0.94±0.12）水平明显升高（t=6.077 ～ 14.974），且感染组各水平低于/ 高于非感染组（t=2.017 ～ 10.688），差异具有统计学意义（均P<0.05）。PROM 胎盘组织中H3K4me3 与H3K27me3 水平呈显著负相关（r=-0.604，P<0.05）；H3K4me3，MLL1，JMJD3 mRNA 水平分别与HCA 组织学分期呈负相关（r=-0.646，-0.489，-0.503，均P<0.05）；H3K27me3，EZH2 mRNA，KDM5B mRNA 水平分别与HCA 组织学分期呈正相关（r=0.632，0.515，0.520，均P<0.05）。当H3K4me3，H3K27me3 截断值分别取0.10%，0.19% 时，两者联合预测PROM 并发HCA 感染的AUC（95%CI）值为0.896（0.882 ～ 0.947），敏感度、特异度分别为92.14% 和86.23%，明显高于两者单一指标诊断。结论 PROM 胎盘组织中H3K4me3，H3K27me3 及修饰酶水平与HCA 感染及其组织学分期密切相关，对并发HCA 感染具有较高的临床预测价值，有望作为临床诊断的新型生物标志物。
Abstract:
Objective To study the expression levels and clinical significance of histone H3 trimethylation at lysine 4 (H3K4me3), histone H3 trimethylation at lysine 27 (H3K27me3) and modifying enzyme in placental tissue of patients with premature rupture of membranes (PROM) with chorioamnionitis. Methods Clinical data of 95 pregnant women treated in the Xi’an Gaoxin Hospital due to PROM from June 2021 to December 2023 were retrospectively collected, and they were divided into infected group and a non-infected group according to whether they were complicated with histological chorioamnionitis(HCA). Another 30 normal pregnant women were selected as the control group. Placental tissues of all subjects were collected and H3K4me3 and H3K27me3 levels were detected, and the expression levels of H3K4me3, H3K27me3 specific methyltransferase [mixed lineage leukemia protein-1(MLL1), Zeste enhancer homolog 2(EZH2)] and demethyltransferase [lysine-specific demethylase 5B(KDM5B), Jumonji domain-containing protein 3(JMJD3)] were detected by quantitative real-time PCR(qRT-PCR). The expression differences of H3K4me3, H3K27me3 and specific modifiers among the three groups and the correlation with the histological stage of HCA were analyzed. The Receiver operating characteristic curve (ROC) was plotted, the Area under curve (AUC) value was calculated, and H3K4me3 was evaluated. Predictive value of H3K27me3 for concurrent HCA infection. Result Compared with the control group, the levels of H3K4me3（0.08%±0.02%，0.12%±0.03% vs 0.25%±0.06%）, MLL1 mRNA（1.32±0.16，1.44±0.23 vs 2.02±0.31）, and JMJD3 mRNA（0.78±0.13, 0.91±0.15 vs 1.53±0.23）in the infected and non-infected groups were significantly decreased（t=10.939 ～ 19.062）, while the levels of H3K27me39（0.23%±0.05%， 0.15%±0.03% vs 0.10%±0.02%）, EZH2 mRNA（1.96±0.26，1.85±0.25 vs 1.15±0.29）and KDM5B （1.46±0.15， 1.35±0.18 vs 0.94±0.12）were significantly increased（t=6.077 ～ 14.974）, and the levels in the infected group were lower/ higher than those in the non-infected group（t=2.017 ～ 10.688）, with statistically significant differences (all P<0.05). There was a significant negatively correlation between H3K4me3 and H3K27me3 levels in placenta tissue of PROM (r=-0.604， P<0.05). The levels of H3K4me3, MLL1 and JMJD3 were negatively correlated with the histological stages of HCA (r=- 0.646，-0.489，-0.503，all P<0.05). The levels of H3K27me3, EZH2 and KDM5B were positively correlated with the histological stages of HCA (r=0.632，0.515，0.520，all P<0.05). The cutoff values of H3K4me3 and H3K27me3 were 0.10% and 0.19%, respectively. The AUC（95%CI） value of the combined prediction of PROM combined with HCA infection was 0.896(0.882 ～ 0.947), and the sensitivity and specificity were 92.14% and 86.23% respectively, which was significantly higher than the diagnosis of a single index. Conclusion The levels of H3K4me3, H3K27me3 and modifying enzymes in the placenta tissue of PROM are closely related to HCA infection and histological stage, which has high clinical prediction value for HCA infection and is expected to be a new biomarker for clinical diagnosis.

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备注/Memo

备注/Memo:
作者简介：宋园（1985-），女，本科，主治医师，研究方向：妇产科围产医学临床研究，E-mail：ducaiyun1016@163.com。
通讯作者：屈小红（1976-）女，本科，主治医师，研究方向：妇产科围产医学临床研究，E-mail：475488918@qq.com。
更新日期/Last Update: 2025-03-15