子宫内膜异位症痛经患者血浆蛋白质组学研究

Study on plasma proteomics in patients of endometriosis dysmenorrhea

目的:应用蛋白质组学方法探讨子宫内膜异位症痛经的生物学标志物及相关发病机制。方法:选择符合纳入及排除标准的子宫内膜异位症痛经寒凝血瘀证患者(内异症组)、原发性痛经寒凝血瘀证患者(痛经组)、健康女性(正常组)为研究对象,每组8例。采集各组受试者月经周期第2天的静脉血浆样本进行蛋白提取、胰酶酶解,采用Label-free定量蛋白质组学技术筛选差异表达蛋白,采用生物信息学的分析方法进行功能注释、关键信号通路富集等。结果:内异症组与正常组共筛选出180个差异表达蛋白,痛经组与正常组共筛选出219个差异表达蛋白。经交集比对后,得出子宫内膜异位症痛经相关差异表达蛋白83个,其中50个蛋白下调,33个蛋白上调。GO富集分析筛选到Wnt信号通路的正调控、平滑肌细胞迁移的正调控等生物学过程。KEGG通路富集分析主要富集到PI3K-Akt信号通路、糖代谢、黏着斑、糖酵解等信号通路。蛋白互作网络及拓扑参数分析显示纤维连接蛋白1(FN1)、磷酸丙糖异构酶1(TPI1)、Ⅰ型胶原蛋白α1链(COL1A1)、转醛醇酶1(TALDO1)为核心差异表达蛋白。结论:子宫内膜异位症痛经的发病机制可能与调节核心差异表达蛋白,参与代谢、免疫、血管生成等关键生物学过程和信号通路,调控细胞增殖、迁移、黏附、凋亡、侵袭等细胞功能有关。

Objective:To investigate the biomarkers and pathogenesis of endometriosis dysmenorrhea by proteomics.Methods:Patients of endometriosis dysmenorrhea with cold coagulation and blood stasis syndrome(endometriosis group),patients of primary dysmenorrhea with cold coagulation and blood stasis syndrome(dysmenorrhea group)and healthy women(normal group)who met the inclusion and exclusion criteria were selected as the research objects,with 8 cases in each group.Venous plasma samples of subjects in each group on the second day of menstrual cycle were collected for protein extraction and trypsin enzymolysis.Label-free quantitative proteomics was used to screen differentially expressed proteins.Functional annotation and key signaling pathways enrichment were carried out by bioinformatics analysis.Results:A total of 180 differentially expressed proteins were screened between endometriosis group and normal group.A total of 219 differentially expressed proteins were screened between dysmenorrhea group and normal group.After intersection comparison,83 differentially expressed proteins related to endometriosis dysmenorrhea were obtained,among which 50 proteins were down-regulated and 33 proteins were upregulated.GO enrichment analysis screened out biological processes such as the positive regulation of Wnt signaling pathway and positive regulation of smooth muscle cell migration.KEGG pathway enrichment analysis mainly concentrated in PI3KAkt signaling pathway,glucose metabolism,focal adhesion,glycolysis and other signaling pathways.The analysis of protein interaction network and topological parameters showed that fibronectin(FN1),triosephosphate isomerase 1(TPI1),collagen typeⅠalpha 1(COL1A1)and transaldolase(TALDO1)were the core differentially expressed proteins.Conclusion:The pathogenesis of endometriosis dysmenorrhea may be related to the regulation of core differentially expressed proteins,the participation of metabolism,immunity,angiogenesis and other key biological processes and signaling pathways,and the regulation of cell proliferation,migration,adhesion,apoptosis,invasion and other cell functions.