Expression Of PD-L1,PD-1,p-S6 And Ki-67 In Lung Adenocarcinoma And Correlation With Clinicopathological Features And Prognosis

Objective:To investigate the expression of PD-L1,PD-1,p-S6 and ki-67 in lung adenocarcinoma and to analyze their relationship with clinicopathological features and prognosis.To find the prognostic factors and to provide more theoretical evidence for predicting prognosis related immunotherapy oflung adenocarcinoma.Methods:Collected from January 1,2013 to December 30,2015 at the First Affiliated Hospital of Dalian Medical University surgical resection of invasive lung adenocarcinoma in 155 cases,paraffin specimens from the pathology archives,and all clinical data integrity.Including acinar 90 cases,lepidi 27 cases,papillary 15 cases,micropapillary 6 cases and solidl7 cases.The expression of PD-L1,PD-1,p-S6 and Ki-67 in lung adenocarcinoma were detected by immunohistochemistry,and all cases were followed up.SPSS 21.0 statistical software was used to analyze the data.The differences of PD-L1,PD-1,p-S6 and Ki-67 expression rates were compared by y2 test.Spearman rank correlation analysis was used to analyze the correlation factors.The single factor survival analysis were computed by the Kaplan-Meier method,the comparison between groups using Log-Rank test.The prognosis multi-factor survival analysis using COX regression model.p-value less than 0.05 were considered significantResult:1.Expression of PD-L1,PD-1,p-S6 and Ki-67 in lung adenocarcinoma and their correlation(1).PD-L1,PD-1,p-S6 and Ki-67 expression in lung adenocarcinoma1).PD-L1 was expressed in lung adenocarcinoma tumor cells(T)and tumor interstitial lymphocytes and macrophages(L).PD-1 was expressed in tumor-infiltrating lymphocytes(TIL),while tumor cells were not expressed.P-S6 and Ki-67 were expressed on the surface of tumor cells2).In 155 cases of lung adenocarcinoma,the positive expression(>10%)rates of PD-L1(T)and PD-L1(L)were 31.6%and 99.4%respectively,the strongexpression positive(≥ 50%)rates were 16.8%and 63.9%.The positive expression rate of PD-1(TIL)was 54.8%and the expression of tumor cells was 0.The positive expression rates of p-S6 and Ki-67 were 75.5%and 76.8%respectively(2).Correlation between PD-L1,PD-1(TIL),p-S6 and Ki-67 expression in lung adenocarcinoma1)PD-L1(L)expression was positively correlated with PD-L1(T)and PD-1(TIL)(P<0.05)2)PD-L1 and PD-1(TIL)were not associated with p-S6 and Ki-67 expression(P>0.05)3)There was no correlation between p-S6 and Ki-67 expression(P>0.05)2.PD-L1,PD-1(TIL),p-S6and Ki-67 expression of the correlation with the clinical parameters of lung adenocarcinoma(1)The expression of PD-LI(T)was correlated with tumor size,lymph node metastasis,pathological type,clinical stage,sex,age,smoking history and serum CEA(P<0.05).PD-L1 expression rate in different pathologic types of lung adenocarcinoma is different(P<0.05),the solid was the highest,which was 70.6%.while thelepidi’s expression was lowest,which was 11.1%(2)PD-1 expression was only associated with lymph node metastasis(P<0.05)(3)The expression of Ki-67 was correlated with tumor size,pleural involvement,vascular thrombus/nerve invasion,pathological type and tumor stage(p<0.05).Subgroup analysis,ki-67 expression in different pathological types was different,micropapillary and solid type’s ki-67 positive expression rates was significantly higher than other types,which were 100%and 94.1%;and lepidi was the lowest,51.9%(p<0.05).(4)The expression of PD-L1(T)was positively correlated with the Ki-67 expression in the micropapillary(rs=1,P<0.01),while that was no correlation between PD-L1(T)and Ki-67 in other types(p>0.05).(5)PD-L1(L)and p-S6 were not associated with gender,age,smoking history,tumor location,tumor size,lymph node metastasis,involving pleural,vascular thrombus and nerve invasion,pathological type,tumor stage and serum CEA(p>0.05).3.Expression of PD-L1,PD-1(TIL),p-S6,Ki-67 and prognosis of lung adenocarcinoma(1).Sngle factor survival analysisshowed thatPD-L1,PD-1(TIL)and Ki-67 expression,lymph node metastasis,vascular thrombosis/nerve invasion,pathological type and tumor stage were related with the survival of lung adenocarcinoma(p<0.05),while p-S6 was not correlated with it(p>0.05).(2).COX multivariate analysis showed that lymph node metastasis,tumor stage and pathological type were independent prognostic risk factors(p<0.05),while PD-L1(T)was not an independent prognostic risk factor for lung adenocarcinoma(p>0.05).Conclusion1.The positive expression rate of PD-L1 in lung adenocarcinoma was 31.6%.PD-L1(T)overexpression is associated with a short survival time,suggesting that immunosuppression has an adverse effect on the patient’s survival,which may be a potential population for immunotherapy.2.PD-L1(T),ki-67 was significantly higher in solid adenocarcinoma,and the prognosis of solid adenocarcinoma was poor,which may be the potential population of immunotherapy.3.In micropapillary lung adenocarcinoma,PD-L1(T)and Ki-67 showed a significant positive correlation,suggesting that the two may play a synergistic role in the development and progression of this subtype4.PD-L1(T),PD-1(TIL)and Ki-67 high expression is the prognostic factors of invasive lung adenocarcinoma5.There was no significant correlation between p-S6 overexpression and PD-L1,PD-1 expression and prognosis in lung adenocarcinoma tissues.