Expression And Significance Of COX-2,PD-L1 And ARG1 In Pituitary Adenoma

Objective:To study the expression of cyclooxygenase-2(COX-2),programmed cell death-ligand 1(PD-L1)and Arginase I(ARG1)in pituitary adenoma(PA)and the mechanism of immune escape in PA.Methods: 55 surgical specimens of pituitary adenoma(PA)(the 25 functionings and the 30 nonfunctionings)were collected from Neurosurgery Department of Jining Medical University Affiliated Hospital,and ten fresh human brain tissues(patients with brain injury undergoing internal decompression)were collected as the control group.The expression of COX-2,PD-L1 and ARG1 in PA was detected by immunohistochemistry and Western blotting.The relationship between the expression of COX-2,PD-L1 and ARG1 was quantitatively analyzed by Image J software.Double immunofluorescence colocalization technique was used to detect the location of COX-2,PD-L1 and ARG1 in PA cells.Results: Compared with normal brain tissue,the protein expression levels of COX-2,PD-L1 and ARG1 in PA increased significantly(P<0.001,<0.001,<0.001).In functioning pituitary adenoma(FPA)and non-functioning pituitary adenoma(NFPA),there was no significant difference in the expression level of COX-2 and PD-L1,but ARG1 was higher(P<0.05)in NFPA.COX-2 expression was higher in the > 50 years age group(P<0.05)than in the ≤50 years age group.In all 30 cases of NFPA,COX-2 expression was higher in the > 50 years age group(P<0.05),but there was no significant difference in FPA.In the gender group,PD-L1 was more expressed in male patients(P<0.05)than in female patients.Quantitative analysis of immune expression showed that:COX-2 protein expression level was positively correlated with PD-L1 and ARG1 protein expression level,and PD-L1 protein expression level was positively correlated with ARG1 protein expression level.Double immunofluorescence confocal imaging showed that COX-2,PD-L1 and ARG1 were all expressed in the cytoplasm of PA cells,and the physical positions of COX-2,PD-L1 and ARG1 were mostly coincident.Conclusions: COX-2,PD-L1 and ARG1 were involved in the immune escape of PA.COX-2 may upregulate the expression of PD-L1,then promote the expression of ARG1,form COX-2-PD-L1-ARG1 pathway,and promote the occurrence and development of PA.Compared with FPA,COX-2-PD-L1-ARG1 pathway plays a more significant role in promoting NFPA immune escape.