Expression And Clinical Significance Of LAG-3、PD-1 And HIF-1α In Non-small Cell Lung Cancer

Objective:To investigate the expression of lymphocyte activation gene-3(LAG-3)、programmed death-1(PD-1)and hypoxia inducible factor-1α(HIF-1α)in non-small cell lung cancer and its clinical significance.Methods:1.A total of 106 NSCLC patients undergoing surgery in Hebei General Hospital between January 2013 and December 2015 were collected.All patients had complete case data and follow-up data.In addition,20 normal lung tissue specimens were collected as controls.2.Immunohistochemical SP method was used to detect the expression of LAG-3,PD-1,and HIF-1αin cancer tissues and adjacent normal tissues.Analyze the relationship and prognosis between the three.Results:1.The relationship between the expression of LAG-3,PD-1,HIF-1αand clinicopathological featuresThe positive rates of LAG-3,PD-1 and HIF-1αin NSCLC tissues and normal tissues were respectively 45.3%(48/106)、33.0%(35/106)、51.9%(55/106);5.0%(1/20)、5.0%(1/20)、20.0%(4/20).LAG-3 expression was associated with pN staging,pTNM staging,lymph node metastasis,nerve infiltration,and vascular tumor emboli.PD-1 expression was associated with smoking status,pN staging,pTNM staging,lymph node metastasis,nerve infiltration,and vascular tumor emboli.HIF-1αexpression was associated with pN stage,pTNM stage,lymph node metastasis,nerve infiltration,and vascular tumor embolus.2.The relationship and prognosis between LAG-3,PD-1,HIF-1αKaplan-Meier survival curve analysis showed that LAG-3 expression was significantly associated with DFS and OS(χ~2=7.210,P=0.007 andχ~2=7.626,P=0.006);PD-1 expression was significantly associated with DFS and OS(χ~2=7.436,P=0.006 andχ~2=6.743,P=0.009);HIF-1αexpression was significantly associated with DFS and OS(χ~2=18.977,P=0.000 andχ~2=17.106,P=0.000).Univariate analysis showed that DFS was associated with differentiation,pN stage,pTNM stage,lymph node metastasis,nerve infiltration,vascular thrombus,LAG-3 positive expression,PD-1 positive expression,and HIF-1αpositive expression(P<0.05);and OS was associated with differentiation,pN stage,pTNM stage,lymph node metastasis,vascular tumor thrombus,LAG-3 positive expression,PD-1 positive expression,HIF-1αpositive expression(P<0.05).Cox multivariate analysis showed that pN staging and vascular tumor embolus were independent factors of poor prognosis of DFS(P<0.05);smoking status,p N staging,lymph node metastasis were independent factors of OS poor prognosis(P<0.05).3.Correlation between LAG-3,PD-1,and HIF-1αexpressionSpearman rank correlation analysis showed that LAG-3 was positively correlated with PD-1 expression(r_s=0.208,P=0.033);LAG-3 was positively correlated with HIF-1αexpression(r_s=0.383,P=0.000);PD-1 was positively correlated with HIF-1αexpression(r_s=0.435,P=0.000).Conclusions:1.The expression of LAG-3,PD-1 and HIF-1αprotein was highly expressed in NSCLC tissues.The expression of LAG-3,PD-1 and HIF-1αprotein was related to pN stage,pTNM stage,lymph node metastasis,nerve infiltration and vascular tumor thrombus.PD-1 expression was associated with smoking status.2.The positive expressions of LAG-3,PD-1,and HIF-1αwere negatively correlated with DFS and OS.PN staging and vascular tumor embolus were independent factors of DFS;smoking status,p N staging and lymph node metastasis were independent factors of OS.3.The expression of LAG-3,PD-1 and HIF-1αin NSCLC tissues was positively correlated with each other.