Expression Of TIM-3、PD-1 And EGFR In Non-small Cell Lung Cancer And Their Relationship With Clinical Characteristics And Prognosis

Objective:By testing T cell immunoglobulin domain and mucin domain-3(TIM-3),Programmed Death-1(PD-1),Epidermal growth factor receptor(EGFR)protein expression in Non-small cell lung cancer(NSCLC)tissues,analyze their clinical pathological characteristics and the relationship with the survival time,and find out the biological factors for the specific therapeutic targets influencing the prognosis and provides a new direction of the research for the NSCLC.Methods:A total of 97 cases of patients with NSCLC receiving surgical treatment in HEBEI GENRAL HOSPITAL from January 2014 to December 2015 were collected.The expression of TIM-3,PD-1,EGFR in97 cases of the NSCLC tissues and 50 cases of adjacent normal lung tissues were detected by immunohistochemical SP method,and the relationship between the expression of TIM-3,PD-1,EGFR and clinicopathological features,Disease-free survival(DFS),Overall survival(OS)of the patients were analyzed.SPSS 21.0 software was used for statistical analysis.Results:1.Relationship between expression of TIM-3,PD-1,EGFR and clinicopathological characteristics.TIM-3,PD-1,EGFR are expressed in cell membrane and cytoplasm in tumor tissues and para-carcinoma normal lung tissues.The positive expression rates of TIM-3,PD-1,EGFR were 52.6%(51/97),46.4%(45/97),64.9%(63/97)in tumor tissues and 10%(5/50),8.0%(4/50),20.0%(10/50)in para-carcinoma normal lung tissues,respectively.The positive expression rates of TIM-3,PD-1,EGFR in the tumor tissues were significantly higher than that in the para-carcinoma normal lung tissues(P<0.001,P<0.001,P<0.001).Expression of TIM-3,PD-1,EGFR were positively correlated with lymph node metastasis(P=0.015,P<0.001,P=0.014)and later TNM staging(P=0.022,P=0.001,P<0.001).TIM-3,PD-1 expression were positively correlated with the degree of differentiation(P=0.001,P<0.001).2.Relationship between TIM-3,PD-1,EGFR and prognosisThe median DFS was 17.00 months and the median OS was 24.00months in 97 patients.The 1,2,3 years DFS rates were in the TIM-3(-)group and(+)group:73.9%,46.7%,27.3%and 51.0%,19.4%,0%(P<0.001);PD-1(-)group and(+)group:75.0%,49.8%,23.9%and46.7%,7.5%,0%(P<0.001);EGFR(-)group and(+)group:73.5%,58.2%,29.5%,and 57.1%,17.2%,5.7%(P<0.001).TIM-3/PD-1 both(-)group and single(+)group and both(+)group:81.3%,59.1%,34.6%and 61.8%,26.5%,0%and 32.3%,8.6%,0%(P<0.001);TIM-3/EGFR both(-)group and single(+)group and both(+)group:82.6%,68.5%,38.5%and 61.8%,27.5%,11.4%and 42.5%,14.6%,0%(P<0.001);PD-1/EGFR both(-)group and single(+)group and both(+)group:81.5%,70.2%,35.5%and 62.5%,23.6%,9.4%and 39.5%,8.3%,0%(P<0.001).The results of univariate analysis showed that degree of differentiation,lymph node state and TNM stage were associated with DFS(P=0.006,<0.001,<0.001).Cox multivariate analysis showed that lymph node state,TNM stage and TIM-3/PD-1were independent factors for prognosis of DFS(P=0.000,0.006,0.001).The 1,2,3 years OS rates were in the TIM-3(-)group and(+)group:80.2%,67.7%,58.4%and 66.7%,32.4%,13.2%(P<0.001);PD-1(-)group and(+)group:86.5%,67.2%,46.8%and 57.2%,23.3%,23.3%(P<0.001);EGFR(-)group and(+)group:79.4%,63.9%,55.9%and69.6%,39.8%,23.8%(P=0.005).TIM-3/PD-1 both(-)group and single(+)group and both(+)group:87.5%,78.0%,66.3%and 76.2%,44.9%,17.5%and 54.8%,20.2%,20.2%(P<0.001);TIM-3/EGFR both(-)group and single(+)group and both(+)group:87.0%,77.7%,68.0%and 70.0%,49.1%,45.3%and 67.5%,31.6%,11.8%(P<0.001);PD-1/EGFR both(-)group and single(+)group and both(+)group:88.9%,73.7%,63.2%and 75.0%,52.6%,30.2%and 60.0%,23.6%,23.6%(P<0.001).The results of univariate analysis showed that age,degree of differentiation,lymph node state and TNM stage were associated with OS(P=0.016,0.005,0.002,<0.001).Cox multivariate analysis showed that TNM stage and TIM-3/PD-1 were independent factors for prognosis of OS(P=0.005,0.001).3.Correlation of TIM-3,PD-1,EGFR expressionSpearman analysis showed that TIM-3 was positively correlated with PD-1 expression(r_s=0.304,P=0.002)and EGFR expression(r_s=0.298,P=0.003).PD-1 was positively correlated with EGFR expression(r_s=0.380,P<0.001).Conclusions:1.The expressions of TIM-3,PD-1,EGFR were higher in the NSCLC tissues than the normal lung tissues,and the positive expressions were correlated with lymph node metastasis and late TNM stage,while the high expression of TIM-3 and PD-1 was correlated with the low degree of differentiation.2.Expression of TIM-3,PD-1,EGFR in NSCLC tissues were positively correlated with each other.3.Positive expressions of TIM-3,PD-1,EGFR,TIM-3/PD-1,TIM-3/EGFR,PD-1/EGFR in the NSCLC tissues were negatively correlated with DFS and OS.TNM staging and TIM-3/PD-1 were independent factors of DFS and OS.Lymph node metastasis was the independent factors of DFS.