Expression And Clinical Significance Of PD-L1 And FOXP3 In Adenocarcinoma Of Esophagogastric Junction(Siewert Type ?)

Objective:The study was to learn expression of programmed death ligand-1(PD-L1)and forkhead box protein 3(FOXP3)in the adenocarcinoma of esophagogastric junction(Siewert type ?)and to explore the relationship between PD-L1/FOXP3 and clinicopathological characters as well asprognosis,which can provide theoretical basis for the immunotherapy of Siewert type ? AEGMethods:131 tumor sections from Siewert type ? AEG received radical esophagogastrectomy and standardized lymphadenectomy in Affiliated Hospital of North Sichuan Medical College from Jan.2012 to Dec.2014 and 20 cases corresponding normal adjacent tissueswere selected.Immunohist-ochemistry was employed to detectedthe expression of PD-L1 and FOXP3.SPSS25.0 software,Chi-square test were performed to analyses the relationship between PD-L1/FOXP3 and clinicopathological parameters,Spearman correlation coefficients analysedthe relationship between PD-L1 expression and FOXP3 expression,univariate and multivariate analysis explored the relationship between clinical indicators and prognosisvia the Cox proportional hazards regression model,Kaplan-Meier method and log-rank test analysed the relationship between expression of PD-L1/FOXP3 and prognosis,a P value of less than 0.05 was considered statistically significant.Results:1.Among the 131 samples,61 cases(46.6%)exhibited PD-L1 expression of Siewert type II AEG,located in the cytoplasm and cell membrane of tumor cells.There was no expression of PD-L1 in 20 cases of normal adjacent tissues(P<0.05).2.The expression of PD-L1 was positively associated with invasion depth of tumor,tumor grade,lymph node metastasis and pTNM stage(P<0.05),but not related to the age,gender,preoperative complications and tumor size of Siewert type ? AEG(P>0.05),3.Among the 131 samples,66 cases(50.4%)exhibited FOXP3 expression of Siewert type ? AEG,which werelocated in the nucleus of tumor infiltrating lymphocytes.There was no expression of FOXP3 in 20 cases of normal adjacent tissues(P<0.05).4.The expression of FOXP3 was positively associated with tumor grade,lymph node metastasisand pTNM stage(P<0.05),but not related to the age,gender,preoperative complications,tumor size and invasion depth of tumor of Siewert type ? AEG(P>0.05).5.There was a positive correlation between the expression of PD-L1 and FOXP3 in Siewert type ? AEG(r=0.253.P<0.05).6.Univariate analysis showed that tumor grade,invasion depth of tumor,lymph node metastasis,pTNM stage,PD-L1 positive expression and FOXP3 positive expression were influencing factors of the poor prognosis of Siewert type ? AEG(P<0.05),while tumor size,operation age,gender,preoperative complications,postoperative complications and postoperative chemotherapy were not related to overall survival(P>0.05).Multivariate analysis indicated that PD-L1/FOXP3 expression,invasion depth of tumor and lymph node metastasis were independently influencing factors of the poor prognosis of Siewert type ? AEG(P<0.05).According to Kaplan-Meier survival curves and log-rank test,the expression of PD-L1 in tumor cells was significantly correlated with overall survival,The 5-year overall survival rate of those with PD-L1 positive expression was 14.8%,while that without expression of PD-Llwas 51.1%(P<0.05).FOXP3 in tumor infiltrating lymphocytes was significantly correlated with the overall survival,The 5-year overall survival rate of FOXP3 positive expression was 18.3%,while that without expression of FOXP3 was 56.9%.(P<0.05).7.According to the expression of PD-L1 and FOXP3,the patients were divided into four types:type I PD-L1(+)/FOXP3(+),type ? PD-L1(+)/FOXP3(-),type ? PD-L1(-)/FOXP3(+),type ? PD-L1(-)/FOXP3(-),Kaplan-Meier survival curves and Log-rank test showed that the prognosis of type ? was the worst,and that of type ? was the best(P<0.05).Conclusions:1.Both PD-L1 and FOXP3 were expressed in Siewert type ? AEG,there was a positive correlation between the expression of PD-L1 and FOXP3.The expression of PD-L1 was significantly correlated with tumor invasion depth of tumor,tumor grade,lymph node metastasis and pTNM stage;The expression of FOXP3 was significantly correlated with tumor grade,lymph node metastasis,and pTNM stage,which indicated that both PD-L1 and FOXP3 were closely related to tumor invasion and metastasis.2.The expression of PD-L1/FOXP3 was negatively correlated with the prognosis of the Siewert type ? AEG,which was an independent factor for the overall survival.The prognosis of the patients with PD-L1/FOXP3 combined expression was the worst.