The Expression Of Mismatch Repair Protein,PD-L1 And PD-1 In Gastric Cancer And Its Clinical Significance

Objective:To investigate the relationship between the expression of programmed cell death-1(PD-1)protein,programmed cell death-Ligand 1(PD-L1),Mismatch Repair(MMR),and clinicopathological characteristics of primary gastric cancer,and provide experimental evidence for the treatment and prognosis of primary gastric cancer.Methods:A total of 176 patients with primary gastric cancer who underwent radical gastrectomy at the Department of Gastrointestinal Surgery,Sichuan Provincial People's Hospital from October 2016 to February 2018 were selected.The clinical pathological datum of patients were collected and followed up.The expressions of mismatch repair proteins MLH1,PMS2,MSH2,MSH6 and immune detectionpoints of PD-1 and PD-L1 in paraffin tissue of patients with primary gastric cancer after surgery were performed.The relationship between the expression of mismatch repair protein in primary gastric cancer and the clinicopathological parameters were analyzed.The singlefactor analysis and the Cox proportional hazard regression model toscreen the independent risk factors for survival time with primary gastric cancer were determined.Results:?.Mismatch repair proteins were positively expressed in the nucleus of tumor cells.The loss rate of mismatch repair protein in 176 cases of gastric cancer tissue was 18.2%(32/176).11 of them(6.3%)had a loss of MMR protein.There were the deficiency of MMR proteins in two cases(10.2%),three MMR proteins defect in two cases(1.1%),and four MMR proteins defect in one(0.6%)patient.?.The loss of MMR protein expression were related to the expression of TNM stage(P=0.047,r=0.567),pathological type of gastric cancer(P=0.039,r=0.628),lymphatic invasion of tumor(P=0.049,r=-0.580),P53(P=0.041,r=-0.612)in gastric cancer patients.There were no significant differences between patients with different gender,age,tumor size,tumor location,tumor differentiation,tumor classification,tumor invasion depth,lymph node metastasis,distal tumor metastasis,and KI67 positive index(P<0.05).?.PD-L1 was positively expressed on the tumor cell membrane.The positive rate of PD-L1 in gastric cancer tumor cells was 13.1%(23/176).The positive expression of PD-L1 was related to the TNM stage of gastric cancer patients(P=0.017,r=0.581)and the pathological type of gastric cancer(P=0.045,r=-0.254),KI67 positive index(P=0.048,r=0.243),tumor vascular invasion(P=0.038,r=0.280),MMR protein expression(P=0.021,r=0.520);but there was no significant difference in patients different with gender,age,tumor size,tumor site,tumor classification,tumor classification,tumor invasion depth,lymph node metastasis,distant metastasis,P53 expression,and lymphatic invasion(P>0.05);D-1 is positively expressed in lymphocytes and tumor cells,and the expression of PD-1 on tumor cells is related to lymph node metastasis(P=0.035)and lymphatic infiltration(P=0.032),and is related to gender,age,tumor size,tumor pathology Type,depth of tumor invasion,TNM stage,and MMR status were not related(P>0.05);PD-1 expression on interstitial lymphocytes was only related to lymph node metastasis(P=0.028)?.Survival analysis:128 patients with a follow-up period of 2 years were included in the survival analysis.The 1-,2-years survival rates of these 128 patients were 98.1%and 92.0%.Univariate analysis showed tumor size(P=0.042),pathological type of gastric cancer(P=0.028),MMR protein expression(P=0.032),PD-L1 expression(P=0.043),KI67 positive index(P=0.039),P53(P=0.032)was related to the prognosis of gastric cancer.The age,gender,tumor location,tumor type,and tumor differentiation of patients were not related to disease-free survival,and the differences were not statistically significant(P>0.05).The factors in the univariate analysis were included in the multivariate Cox proportional hazards model for multivariate regression analysis.The results showed the the independent factors affecting the survival of patients with gastric cancer were PD-L1(P=0.033),MMR protein(P=0.046),and TNM stage(P=0.000),P53(P=0.032).Patients with primary gastric cancer were divided into 4 groups according to the expression of PD-L1 and MMR proteins.Among them,patients with both PD-L1 negative expression and loss of mismatch repair protein had better prognosis.Conclusion:The expression of MMR protein and PD-L1 protein is closely related to the clinicopathological characteristics and prognosis of gastric cancer,and it is of great significance in evaluating the biological behavior and prognosis of gastric cancer.