Expression And Clinical Significance Of NRP-1 In EBV-Associated Lymphoma

OBJECTIVE:Neuropilin-1(NRP-1)is a kind of type I transmembrane glycoprotein on the cell surface.NRP-1,which promotes angiogenesis and tumor growth,plays positive roles in the tumorigenesis and tumor progression of various tumors.However,few relevant research of NRP-1 in epstein-barr virus(EBV)-associated lymphoma was reported.In order to provide clinical basis for the exploration of targeted therapy of EBV-associated lymphoma,this study investigated the level of NRP-1 expression and explored its association with clinicopathological features in EBV-associated lymphoma,and the prognosis of patients with lymphoma was also evaluated.METHODS:A total of 111 cases which diagnosed lymphoma were chosen,including 40 cases of NK/T-cell lymphoma(NKTCL),29 cases of Hodgkin's lymphoma(HL),31 cases of diffuse large B-cell lymphoma(DLBCL)and 11cases of anaplastic large cell lymphoma(ALCL).In addition,20 cases of normal lymphoid reactive hyperplasia were selected.The in situ hybridization technique was used to detect the expression of EBV-encoded RNA(EBER)in the lymphoma tissues,and the immunohistochemical technique was applied to examine the expression of NRP-1 in the lymphoma and lymphoid reactive hyperplasia tissues.At the same time,the level of vascular endothelial growth factor 165(VEGF165),VEGF receptor 2(VEGFR2),latent membrane protein 1(LMP1),CD34 and Ki67 expression were detected with immunohistochemical technique in the lymphoma tissues.The differential expression of NRP-1 in EBV-positive lymphoma,EBV-negative lymphoma and lymphoid reactive hyperplasia tissues was analyzed.The correlations of NRP-1 and EBV with clinicopathological parameters of lymphoma were analyzed,and the prognostic influence of NRP-1 on lymphoma was evaluated in the last.RESULTS:Positive EBER expression was found in 62(55.9%,62/111)of111 cases of lymphoma tissue.EBER was detected in all of the NKTCL patients,and the positive rate of EBER in HL was 75.9%(22/29),while EBER was negatively expressed in DLBCL and ALCL patients.NRP-1 expression was significantly higher in lymphoma than in lymphoid reactive hyperplasia(?~2=5.494,P=0.019),and the positive expression rate of NRP-1 was higher in EBER-positive lymphoma than in EBER-negative lymphoma(?~2=5.4554,P=0.018).Comprehensive analysis showed the differential expression of NRP-1in NKTCL,HL,DLBCL and ALCL(?~2=9.161,P=0.027).Overexpression of NRP-1 was associated with positive EBER expression(?~2=5.554,P=0.018;r=0.224,P=0.018),high VEGF165 expression(?~2=8.122,P=0.004;r=0.270,P=0.004)and overexpression of VEGFR2(?~2=8.596,P=0.003;r=0.278,P=0.003).Positive EBER expression in the four types of lymphoma was related to male patients(?~2=13.835,P<0.001;r=0.353,P<0.001),high expression of LMP1 protein(?~2=65.538,P<0.001;r=0.768,P<0.001),overexpression of VEGFR2(?~2=20.766,P<0.001;r=0.433,P<0.001)and high CD34 expression(?~2=4.919,P=0.027;r=0.219,P=0.027).While negative correlation was found between EBER and clinical III-IV stage(?~2=5.363,P=0.021;r=-0.220,P=0.020),high Eastern Cooperative Oncology Group(ECOG)score(?~2=4.420,P=0.036;r=-0.200,P=0.036)and international prognostic index(IPI)score(?~2=13.444,P<0.001;r=-0.405,P<0.001).Overall survival(OS)and progression-free survival(PFS)of patients with lymphoma were evaluated,and overexpression of NRP-1 was an independent prognostic role for estimating OS[risk ratio(RR)=3.005,95%CI:1.229-7.384,P=0.016]and PFS(RR=2.440,95%CI:1.068-5.572,P=0.034)of non-Hodgkin lymphoma(NHL).CONCLUSION:NRP-1,which is overexpressed in lymphoma,reveals higher positive rate in the EBV-positive lymphoma.Moreover,overexpression of NRP-1 is a risky independent prognostic factor of NHL patients.High NRP-1expression is closely associated with EBV infection and angiogenesis,and NRP-1 is expected to become a prognostic indicator of EBV-associated lymphoma.