The Research Of KDR, MVD, PD-L1 And PD-1 In Peripheral T-cell Lymphoma

Objective: To detect the expression of vascular endothelial growth factor receptor(KDR), micro-vascular density(MVD), programmed death 1-ligad(PD-L1) and programmed cell death factor-1(PD-1) and assess the relationship between the expression of above proteins in peripheral T-cell lymphoma( PTCL) with their clinic-pathological characteristics and prognostic significance. To explore their roles in tumorigenesis and progression of PTCL, and mayprovide a rationale for immune-therapy in PTCL. Methods:Collect 51 specimens of PTCL( PTCL group) and 20 specimens of lymph node optimum pathology(contrast group), then analysis the expressions of KDR, MVD, PD-L1 and PD-1 in tissues with an elivison two-step immune-histochemistry. All cases of PTCL were followed-up. Statistical analysis was performed using statistical software SPSS 19.0.Chisquare test was used to compare the differential expressions of KDR, MVD, PD-L1 and PD-1 in PTCL group and control group, and to compare therelationship between the expression of KDR, MVD, PD-L1 and PD-1 and clinic-pathological characteristics. The correlation analysis was based on spearman correlation analysis. Survivalcurves were calculated according to Kaplan-Meier method.P values lower than 0.05 was considered as statistically significant. Results:(1) KDR and MVD expression positive rate in contrast group was 30.0%(6/20),15.0%(3/20)respectively and 66.7%(34/51),51.0%(26/51)respectively in PTCL group. The difference was statistically significant,(P(27)0.05). The KDR and MVD expression was significantly associated with age,(P(27)0.05). The KDR and MVD expression was no significantly associated with sex,peripheral lactate dehydrogenase(LDH)levels, clinical stages, performance status(PS)score, extranodal involvement, B symptoms, bone marrow involvement, international prognostic index( IPI) score and different subtypes(P(29)0.05).The KDR expression showed no correlation with the expression of MVD in PTCL(r(28)0.055,P(28)0.699). After two cycles of CHOP or ECHOP treatments, the response rate(RR)in KDR negative groupwas higher than positive group(70.6%vs55.9%). But the difference was not statistically significant,(c2=1.028,P(28)0.311).The RR in MVD negative group was higher than positive group(68.0%vs57.7%).The difference was not statistically significant(c2=0.579,P(28)0.447). The media OS in KDR negative group was higher than positive group(24.9Mvs19.4M). But it was not statistically significant(c2=0.849,P(28)0.357). The media OS in MVD negative group was higher than positive group( 27.1Mvs15.7M). It was statistically significant(c2=13.222,P(27)0.01).(2)The results about PD-L1 and PD-1 were listed as follows: PD-L1 and PD-1 positive expression rate in contrast group was 35.0%( 7/20), 25.0%( 5/20) respectively, and 74.5%(38/51),66.7%(34/51) respectively in PTCLgroup. The difference was statistically significant,(P(27)0.05). Only the difference between positive expression rate of PD-L1 and PD-1 and peripheral LDH levels was statistically significant,(P(27)0.05). It no significantly associated withpositive expression rate of PD-L1 and PD-1 and sex, age, clinical stages, PS score, extranodal involvement, B symptoms, bone marrow involvement, IPI score and different subtypes,(P(29)0.05). The expression of PD-L1 showed a positive correlation with the expression of PD-1 in PTCL(r(28)0.732, P(27)0.001). After two cycles of CHOP or ECHOP treatments, the RR in PD-L1 negative groupwas higher than positive group(84.6%vs47.4%). The difference was statistically significant(c2=5.478,P=0.019). The RR in PD-1 negative groupwas higher than positive group( 82.4%vs44.1%). The difference was statistically significant(c2=6.755,P=0.009). The media OS in PD-L1 negative group was higher than positive group(29.8 Mvs17.6M). The difference was statistically significant(c2=4.413,P=0.036). The media OS in PD-L1 positive weakly group, positive moderately group and positive stronglygroup is lower and lower(23.5M vs 20.1M vs 11.4M). The difference was statistically significant(c2=18.961,P(27)0.001).The media OS in PD-1 negative group was higher than positive group(29.8 Mvs17.6M). The difference was statistically significant(c2=8.293,P=0.004).The media OS in PD-1 positive weakly group, positive moderatelygroup and positive strongly group is lower and lower(22.0M vs 16.0M vs 10.9M). The difference was statistically significant(c2=23.666,P(27)0.001).(3) The expression of MVD showed no correlation with the expression of PD-L1 in PTCL(r(28)0.146,P(28)0.305). Conclusion: KDR, MVD, PD-L1 and PD-1 may be related to the disease occurrence, progression and poor prognosis. However, angiogenesis and immune suppression is unrelated in the PTCL development. The high expression levels of PD-L1 and PD-1 in PTCL were closely related with short-term survival. The positive expression group has a lower RR. And the stronger expression,the shorter survivor. They could be factors to judge a bad clinical effect and a poor prognosis.