摘要
目的探讨多囊卵巢综合征(polycystic ovary syndrome,PCOS)患者外周血程序性细胞死亡蛋白1(programmed cell death protein 1,PD-1)和其配体PD-L1表达水平与细胞因子相关性。方法利用GEO数据库中GSE54248数据集筛选出PCOS中差异表达PD-1/PD-L1通路相关基因,对其进行GO和KEGG通路富集分析。采用病例对照研究,选取2022年1月至2023年6月期间在新疆医科大学第一附属医院生殖医学中心就诊的105例PCOS患者(记为PCOS组)和109例非PCOS患者(记为对照组)作为研究对象,利用QBPlex流式高通量多因子检测技术检测两组外周血PD-L1、PD-L2、PD-1和细胞因子表达水平。采用Pearson法进行相关性分析。结果PCOS组患者外周血中PD-1水平[2.890(0.020,4.540)ng/L]显著低于对照组[3.370(2.460,4.360)ng/L,P=0.008];PD-L1水平[9.820(8.860,10.880)ng/L]显著低于对照组[10.410(9.700,11.160)ng/L,P=0.001];PD-L2表达水平在两组间差异无统计学意义(P>0.05)。在GSE54248数据集筛选出26个差异表达基因,主要富集在PD-1/PD-L1通路、1型T辅助细胞(T helper cell 1,Th1)和2型T辅助细胞(T helper cell 2,Th2)分化、参与炎症反应的细胞因子的产生等通路。与对照组相比较,PCOS组患者外周血中白细胞介素(interleukin,IL)-5、IL-9、IL-25、IL-10、生长刺激表达基因2(growth stimulation expressed gene 2,ST-2)和颗粒酶B(Granzyme B)浓度显著降低,IL-8、IL-1RA和肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)浓度显著升高,差异均具有统计学意义(均P<0.05)。PD-1与IL-1RA、ST-2和TNF-α水平呈正相关(r=0.270,P=0.005;r=0.213,P=0.029;r=0.291,P=0.003),与IL-9、IL-25和Granzyme B水平呈负相关(r=-0.322,P<0.001;r=-0.211,P=0.031;r=-0.369,P<0.001)。PD-L1与IL-9、IL-25和Granzyme B水平呈正相关(r=0.254,P=0.009;r=0.330,P<0.001;r=0.340,P<0.001),与IL-10水平呈负相关(r=-0.373,P=0.009)。结论PCOS患者外周血PD-1和PD-L1下调表达,可能与Th1/Th2细胞因子失衡相关,是治疗PCOS的潜在分子生物�
Objective To investigate the association between programmed cell death protein 1(PD-1)and its ligand PD-L1 and cytokines in patients with polycystic ovary syndrome(PCOS).Methods Using the GSE54248 dataset from the GEO database,differentially expressed PD1/PD-L1 pathway-related genes in PCOS were identified and subjected to GO and KEGG pathway enrichment analysis.In this case-control study,totally 105 patients with PCOS(named PCOS group)and 109 non-PCOS patients(named control group)who were treated at the Reproductive Assisted Reproduction Center of the First Affiliated Hospital of Xinjiang Medical University from January 2022 to June 2023 were recruited.The QBPlex flow cytometry high-throughput multiplex assay was utilized to assess the peripheral blood levels of PD-L1,PD-L2,PD-1,and cytokines in PCOS group and control group.Pearson's method was used for correlation analysis.Results In PCOS group,the PD-1 level in peripheral blood[2.890(0.020,4.540)ng/L]was significantly lower than that of control group[3.370(2.460,4.360)ng/L,P=0.008],the PD-L1 level[9.820(8.860,10.880)ng/L]was lower than that in control group[10.410(9.700,11.160)ng/L,P=0.001].There was no significant difference in the expression level of PD-L2 between the two groups(P>0.05).From the GSE54248 dataset,26 differentially expressed genes were identified,primarily enriched in the PD-1/PD-L1 pathway,Th1 and Th2 cell differentiation,and pathways associated with the production of cytokines involved in inflammatory responses.Compared with control group,PCOS group exhibited a significant decrease in the peripheral blood concentrations of interleukin(IL)-5,IL-9,IL-25,IL-10,growth stimulation expressed gene 2(ST-2),and Granzyme B,and a significant increase in IL-8,IL-1RA,and tumor necrosis factor-α(TNF-α)levels,with all differences being statistically significant(all P<0.05).PD-1 exhibited positive correlations with the levels of IL-1RA,ST-2,and TNF-α(r=0.270,P=0.005;r=0.213,P=0.029;r=0.291,P=0.003),while it exhibited negative correlations with the levels
作者
韩锐
巩晓芸
朱玥洁
李奇凤
叶尔登切切克
丁剑冰
腊晓琳
Han Rui;Gong Xiaoyun;Zhu Yuejie;Li Qifeng;Ye Erdengqieqieke;Ding Jianbing;La Xiaolin(Department of Prenatal Diagnosis,the First Affiliated Hospital of Xinjiang Medical University,Urumqi 830054,China;Center for Reproductive Medicine,the First Affiliated Hospital of Xinjiang Medical University,Urumqi 830054,China;Xinjiang Pediatric Research Institute,Urumqi 830054,China;Department of Immunology,School of Basic Medical Sciences,Xinjiang Medical University,Urumqi 830000,China)
出处
《中华生殖与避孕杂志》
CAS
CSCD
北大核心
2024年第5期480-487,共8页
Chinese Journal of Reproduction and Contraception
基金
新疆维吾尔自治区自然科学基金(2022D01C468)。
