Expression levels of PD-1 and PD-L1 in peripheral blood and their correlation with cytokines in patients with polycystic ovary syndrome
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 of IL-9,IL-25,and Granzyme B(r=-0.322,P＜0.001;r=-0.211,P=0.031;r=-0.369,P＜0.001).PD-L1 demonstrated positive correlations with the levels of IL-9,IL-25,and Granzyme B(r=0.254,P=0.009;r=0.330,P＜0.001;r=0.340,P＜0.001),and a negative correlation with IL-10 level(r=-0.373,P=0.009).Conclusion The expression of PD-1 and PD-L1 in the peripheral blood of PCOS patients is down-regulated,which may be associated with an imbalance in Th1/Th2 cytokines and serve as potential molecular biomarkers for the treatment of PCOS.
Polycystic ovary syndromeProgrammed cell death 1Programmed cell death ligand 1Cytokines
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