血清TMT标记定量蛋白质组学对多囊卵巢综合征病因研究

Study on the etiology of polycystic ovary syndrome using serum tandem mass tag-based quantitative proteomics

目的通过应用串联质谱标签(tandem mass tag, TMT)联合液相色谱-串联质谱(liquid chromatography/tandem mass spectrometry, LC-MS/MS)技术、差异表达蛋白及其相关生物通路对多囊卵巢综合征(polycystic ovarian syndrome, PCOS)患者病因研究。方法本研究纳入20例PCOS患者作为PCOS组,18例正常女性作为对照组。通过TMT联合LC-MS/MS检测所有研究对象的空腹血清样本,对数据进行统计学和生物信息学分析。结果鉴定了38个差异表达蛋白质,其中21个蛋白在PCOS中表达上调(FC≥1.2,P<0.05),17个在PCOS中表达下调(FC≤0.83,P<0.05)。采用京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes, KEGG)和Reactome对差异表达蛋白进行富集分析,分别富集到18个和78个通路。将两个数据库富集分析结果整合,均发现补体级联反应的富集通路,共同涉及的差异表达蛋白为甘露糖结合蛋白(mannose-binding protein, MBL)。结论 PCOS患者体内可能存在补体系统的过度激活,差异蛋白MBL可能是其中的关键致病因子。

Objective To study the etiology of patients with polycystic ovary syndrome(PCOS) by using tandem mass tag(TMT) combined with liquid chromatography/tandem mass spectrometry(LC-MS/MS), differentially expressed proteins and associated biological pathways. Methods Twenty patients with PCOS were enrolled into this study to serve as the PCOS group, and 18 healthy women were considered as the control group. The statistical and bioinformatics data were analyzed using all fasting serum samples detected by TMT and LC-MS/MS. Results Thirty-eight differential expression proteins were identified with 21 up-regulated expression(FC≥1.2, P<0.05) and 17 down-regulated expression(FC≤0.83, P<0.05) in PCOS. These proteins were enriched using Kyoto Encyclopedia of Genes and Genomes(KEGG) and Reactome to 18 and 78 pathways, respectively. Integrating two databases enrichment analyses found the enrichment pathway of complement cascade reaction, and the differential expression protein common involved in these databases was mannose-binding protein(MBL). Conclusion PCOS patients may have overactivation in the complement system in which the differential protein MBL may be a key pathogenic factor.