基于子宫内膜异位症患者异位子宫内膜组织代谢特征的非靶向代谢组学分析

doi:10.13481/j.1671-587X.20260318

吉林大学学报(医学版) ›› 2026, Vol. 52 ›› Issue (3): 755-763.doi: 10.13481/j.1671-587X.20260318

基于子宫内膜异位症患者异位子宫内膜组织代谢特征的非靶向代谢组学分析

王青云¹,王青元¹,李青¹,何晔²,王文艳¹,卫兵¹()

^1.安徽医科大学第二附属医院妇产科，安徽合肥 230601
^2.安徽医科大学第一附属医院妇产科，安徽合肥 230601

收稿日期:2025-09-03 接受日期:2025-11-02 出版日期:2026-05-28 发布日期:2026-06-08
通讯作者: 卫兵 E-mail:1191495067@qq.com
作者简介:王青云（1982-），女，安徽省合肥市人，副主任医师，医学硕士，主要从事子宫内膜异位症及妇科内分泌疾病方面的研究。
基金资助:
国家自然科学基金青年基金项目(82301896);安徽省科技厅自然科学基金项目(2008085MH283)

Non-targeted metabolomics analysis based on metabolic characteristics of ectopic endometrium tissue of patients with endometriosis

Qingyun WANG¹,Qingyuan WANG¹,Qing LI¹,Ye HE²,Wenyan WANG¹,Bing WEI¹()

^1.Department of Obstetrics and Gynecology，Second Affiliated Hospital，Anhui Medical University，Anhui Province，Hefei 230601，China
^2.Department of Obstetrics and Gynecology，First Affiliated Hospital，Anhui Medical University，Anhui Province，Hefei 230601，China

Received:2025-09-03 Accepted:2025-11-02 Online:2026-05-28 Published:2026-06-08
Contact: Bing WEI E-mail:1191495067@qq.com

摘要/Abstract

摘要：

目的采用非靶向代谢组学技术探索子宫内膜异位症（EMs）患者异位子宫内膜组织的特征性代谢物，阐明疾病发生发展中的关键代谢调控网络。方法收集2024年1月—2025年1月行手术治疗的91例EMs患者（EMs组）配对的异位和在位子宫内膜组织及63例非EMs患者（非EMs组）的正常子宫内膜组织，采用超高效液相色谱-质谱联用技术（UPLC-MS/MS）进行非靶向代谢组学检测分析。通过R（v4.3.0）软件进行数据统计分析，结合主成分分析（PCA）和正交偏最小二乘法判别分析（OPLS-DA）等多元统计分析方法筛选疾病特征性代谢产物，并采用京都基因与基因组百科全书（KEGG）数据库进行代谢通路富集分析。结果共收集245例子宫内膜组织，其中EMs患者配对的异位和在位子宫内膜组织各91例，正常子宫内膜组织63例，EMs组患者平均年龄为（37.10±3.26）岁，非EMs组患者平均年龄为（38.85±4.67）岁。所有样本共鉴定出2 116种代谢物，其中EMs患者中，与在位子宫内膜比较，异位子宫内膜共有247种代谢物上调，161种代谢物下调；与同期非EMs患者正常子宫内膜比较，EMs患者异位子宫内膜共有412种代谢物上调，97种代谢物下调；与非EMs患者正常子宫内膜比较，EMs患者在位子宫内膜共有94种代谢物上调，65种代谢物下调。与EMs患者在位子宫内膜和非EMs患者正常子宫内膜比较，EMs患者异位子宫内膜共有以6-乙酰氨基-3-氧代己酸酯为代表的163种代谢物上调，以阿洛沙敏为代表的39种代谢物下调。KEGG代谢通路分析，组胺、酪胺、多巴胺和棕榈酰乙醇胺等上调的代谢物显著富集于神经活性配体-受体相互作用通路（P<0.05）。结论 EMs患者异位子宫内膜存在显著代谢重编程，其中以6-乙酰氨基-3-氧代己酸酯为代表的代谢物在异位子宫内膜中明显升高，上调代谢物显著富集于神经活性配体-受体相互作用通路。

关键词: 子宫内膜异位症, 非靶向代谢组学, 代谢物, 代谢通路, 京都基因与基因组百科全书, 富集分析

Abstract:

Objective To explore the characteristic metabolites in ectopic endometrium tissue of the patients with endometriosis （EMs） based on non-targeted metabolomics technology， and to clarify the key metabolic regulatory networks in the occurrence and development of the disease. Methods Paired ectopic and eutopic endometrium tissues from 91 EMs patients who（EMs group） underwent surgical treatment from January 2024 to January 2025， and normal endometrium tissue from 63 non-EMs patients（non-EMs group） were collected. Ultra-high performance liquid chromatography-tandem mass spectrometry （UPLC-MS/MS） was used for non-targeted metabolomics detection and analysis. R （v4.3.0） software was used for statistical analysis of the data； principal component analysis （PCA） and orthogonal partial least squares discriminant analysis （OPLS-DA） were used to screen the characteristic metabolites of the disease； and Kyoto Encyclopedia of Genes and Genomes （KEGG） database was used for metabolic pathway enrichment analysis. Results A total of 245 endometrium tissue samples were collected， including 91 paired ectopic and eutopic endometrium tissue samples from the EMs patients and 63 normal endometrium tissue samples. The average age of patients in EMs group was （37.10±3.26） years old， and that of non-EMs group was （38.85±4.67） years old. A total of 2 116 metabolites were identified in all samples. Among the EMs patients， compared with eutopic endometrium tissue， 247 metabolites were up-regulated and 161 metabolites were down-regulated in ectopic endometrium tissue； compared with normal endometrium tissue of non-EMs patients， 412 metabolites were up-regulated and 97 metabolites were down-regulated in ectopic endometrium tissue of EMs patients； compared with normal endometrium tissue of non-EMs patients， 94 metabolites were up-regulated and 65 metabolites were down-regulated in eutopic endometrium tissue of EMs patients. Compared with both eutopic endometrium tissue of EMs patients and normal endometrium tissue of non-EMs patients， 163 metabolites represented by 6-acetamido-3-oxohexanoate were up-regulated， and 39 metabolites represented by alloxamine were down-regulated in ectopic endometrium tissue of EMs patients. KEGG metabolic pathway analysis showed that the up-regulated metabolites such as histamine， tyramine， dopamine and palmitoylethanolamide were significantly enriched in the neuroactive ligand-receptor interaction pathway （P<0.05）. Conclusion There is significant metabolic reprogramming in the ectopic endometrium tissue of EMs patients. Among them， metabolites represented by 6-acetamido-3-oxohexanoate are significantly increased in ectopic endometrium tissue， and the up-regulated metabolites are significantly enriched in the neuroactive ligand-receptor interaction pathway.

Key words: Endometriosis, Non-targeted metabolomics, Metabolite, Metabolic pathway, Kyoto Encyclopedia of Genes and Genomes, Enrichment analysis

中图分类号:

R711.71

王青云,王青元,李青,何晔,王文艳,卫兵. 基于子宫内膜异位症患者异位子宫内膜组织代谢特征的非靶向代谢组学分析[J]. 吉林大学学报(医学版), 2026, 52(3): 755-763.

Qingyun WANG,Qingyuan WANG,Qing LI,Ye HE,Wenyan WANG,Bing WEI. Non-targeted metabolomics analysis based on metabolic characteristics of ectopic endometrium tissue of patients with endometriosis[J]. Journal of Jilin University(Medicine Edition), 2026, 52(3): 755-763.

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参考文献 26

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Clinical characteristic	n	Age（years）	BMI（kg·m^-2）	ASRM^astage
Clinical characteristic	n	Age（years）	BMI（kg·m^-2）	Ⅰ	Ⅱ-Ⅲ	Ⅳ
EMs	91	37.10±3.26	21.80±1.82	2	39	50
Non-EMs	63	38.85±4.67	22.05±1.70	—	—	—
P		0.094	0.795

Group	Number of differential metabolites
Group	Up-regulated	Down-regulated	Total
Ectopic vs eutopic	247	161	408
Ectopic vs normal	412	97	509
Eutopic vs normal	94	65	159

Metabolite	Category	Molecular formula	Log₂FC	P	VIP
Malonic semialdehyde	Carbohydrate	C₃H₄O₄	2.51	0.001	1.992
Glyoxylic acid	Carboxylic acid	C₂H₂O₃	2.40	<0.001	2.166
2-Methylbutyrylglycine	Amino acids, peptides and their analogues	C₇H₁₃NO₃	2.16	<0.001	2.161
Imidazole 4-formaldehyde	Iminazole	C₅H₆N₂O	1.05	<0.001	2.158
6-acetamino-3-oxohexanoate	-	C₈H₁₃NO₄	3.45	<0.001	2.172
4-hydroxy-5-phenyltetrahydro-1,3-oxazine-2-one	-	C₁₀H₁₁NO₃	2.43	<0.001	2.168
N-acetyl-L-phenylalanine	Amino acids, peptides and their analogues	C₁₁H1₃NO₃	1.20	0.003	2.082
L-2-aminethylserine phosphate	Amino acids, peptides and their analogues	C₅H1₃N₂O₆P	2.89	<0.001	2.186
Alosetron	Carbohydrate	C₂₅H₄₂N₄O₁₄	-2.77	<0.001	2.043
3-Oxo-octanoic CoA	Fatty alkyloxy esters	C₂₉H₄₈N7O₁₈P₃S	-4.15	0.001	1.980

KEGG number	Name	P	Impact	Name of differential metabolite
Hsa05030	Cocaine addiction	0.033	0.250	L-tyrosine, Dopamine
Hsa00630	Acetaldehyde and dicarboxylic acid metabolism	0.091	0.208	Acetaldehyde, dihydroxyacetone phosphate, D-glycerate-3- phosphate, glycerate phosphate, malonate semialdehyde
Hsa05031	Amphetamine addiction	0.051	0.200	L-tyrosine, Dopamine
Hsa05034	Alcohol dependence	0.051	0.200	L-tyrosine, Dopamine
Hsa04917	Prolactin signaling pathway	0.061	0.181	L-tyrosine, Dopamine
Hsa04721	Synaptic vesicle circulation	0.072	0.166	Histamine, Dopamine
Hsa04728	Dopaminergic synapses	0.072	0.166	L-tyrosine, Dopamine
Hsa04080	Neuroactive ligand-receptor interactions	0.003	0.132	Histamine, Tyramine, Cortisol, sphingomyelin-1-phosphate, Thyroxine, Dopamine, Palmitoyl ethanolamine
Hsa04974	Protein digestion and absorption	0.098	0.105	L-tyrosine, Histamine, L-isoleucine, Tyramine
Hsa00071	Fatty acid degradation	0.117	0.129	3-Oxoheptanoacyl-CoA, Tetradecanoacyl-CoA, Dodecano-2,6- dienoyl-CoA, 3,6-dodecanoyl-CoA

基于子宫内膜异位症患者异位子宫内膜组织代谢特征的非靶向代谢组学分析

Non-targeted metabolomics analysis based on metabolic characteristics of ectopic endometrium tissue of patients with endometriosis

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