The Impact Of Radiotherapy On Programmed Death Ligand-1expression In Locally Advanced Rectal Cancer And Analysis Of Prognostic Factors

ObjectiveUsing the methods of immunohistochemical to evaluate the expression of programmed death ligand-1(PD-L1)in locally advanced rectal cancer(LARC)and provide a theoretical support for the combination of radiochemotherapy and PD-1/PD-L1 pathway blockade.We also analyzed the prognostic factors and evaluated the prognostic value of PD-L1 expression in LARC.Methods and MaterialsOne hundred and twenty LARC patients were enrolled in this study,form March2006 to October 2015.All patients were diagnosed as locally advanced disease(clinically T3/T4,or any T category and N positive)according to the 7th Edition AJCC(American Joint Committee on Cancer)Staging Guidelines.Immunohistochemistry were used to detect the expression of PD-L1 in LARC.SPSS was used to perform the statistical analyses,chi-square or fisher test were used to analyzed the clinicopathological characteristics,Kaplan-Meier method and Cox regression model were used to analyzed the survival.Results1)The expression rate of PD-L1 on tumor cells(TCs)and tumor stromal cells(TSs)in radiotherapy group was 17.9% and 55.2%,which was higher than those in non-radiotherapy group(5.7% and 39.6%).Yet,only the difference of TSs in two group was significant(P=0.044).No statistical significant difference were found between the short-term radiotherapy group and long-term radiotherapy group related to PD-L1 expression.2)No correlation were found between each group in PD-L1 expression on TCs and TSs(P>0.05).3)The expression of PD-L1 on TCs was not associated with patients' clinicopathological characteristics,and patients' yp T stage was significantly associated with TSs PD-L1 expression(P=0.033).4)The 5-year disease free survival(DFS)and 5-year overall survival was 63.7%(95%CI,53.5%-73.9%)and 72.2%(95%CI,63.2%-81.2%),respectively.5)Kaplan-Meier survival analysis showed that the PD-L1 expression was not correlated with DFS and OS(P > 0.05).6)The univariate analyses showed that ypT stage(P=0.016),yp N stage(P=0.002),cancer embolus(P=0.013),surgery method(P=0.031)and radiotherapy(P=0.020)were associated with DFS significantly.yp N stage(P=0.001),cancer embolus(P=0.001)and differentiation(P=0.050)were associated with OS,respectively.When using multivariate analysis,we found that only yp N stage(P=0.043)and radiotherapy(P=0.035)were significantly associated with DFS,yp N stage(P=0.006)and cancer embolus(P=0.020)were significantly associated OS.Conclusions1)Patients in radiotherapy group had a higher PD-L1 expression on TCs than those in non-radiotherapy group(17.9% vs.5.7%,P=0.044)indicating that neoadjuvant radiotherapy might upregulate the PD-L1 expression on TCs in LARC patients treated with pre-operative radiotherapy.2)Patients' yp T stage was significantly associated with TSs PD-L1 expression,early stage(T1/T2)patients had a higher PD-L1 expression than advanced stage(T3/T4),which indicate that TSs PD-L1 expression might be a favor prognotic factor for LARC.3)PD-L1 expression had no correlation with patients prognosis in our study,more research should be performed to evaluate its prognosis value.4)In patients with LARC,ypN stage and radiotherapy was the indepent prognostic factors affecting DFS,ypN stage and cancer embolus was the indepent prognostic factors affecting OS.