Expressions And Clinical Significances Of P-gp And CYP3A4in Diffuse Large B-cell Lymphoma

Objective： To study the expression of P-glycoprotein (P-gp) andcytochromeP4503A4（CYP3A4） in Diffuse large B-cell lymphoma(DLBCL）; toexplore the role of the two protein in multidrug resistance and the clinical significancein DLBCL.Methods： This work selected60cases of DLBCL paraffin wax samples,Immunohistochemistry is used to examine the expression of P-gp, CYP3A4respectively.the relation-ships between P-gp, CYP3A4and clinicopathological parameters,Chemosensitivity and prognosis of DLBCL cases were analyzed.Results：1. The positive expression rate of P-gp in DLBCL tissues (33.3%) is significantlyhigher than that in the reactive hyperplasia lymphoid tissues (10.0%)(P<0.05). Theexpression of P-gp is closely related to Ann Arbor stage, extranodal involvement site inDLBCL (P<0.05), but not related to age, B symptoms, LDH level, and PS score (P＞0.05).2. The positive expression rate of CYP3A4in DLBCL tissues (58.3%) issignificantly higher than that in the reactive hyperplasia lymphoid tissues (15.0%)(P<0.05). The expression of CYP3A4has no relationship to age, Ann Arbor stage, Bsymptoms, LDH level, extranodal involvement site, PS score in DLBCL (P＞0.05).3. Significant positive correlation are found between the expressions of P-gpand CYP3A4in DLBCL tissues(rs=0.392，P<0.05).4. The chemotherapy ORR (85.0%) is significantly higher in P-gp-team than thatin P-gp+team (35.0%)(P<0.05).The chemotherapy ORR (84.0%) is significantlyhigher in CYP3A4-team than that in CYP3A4+team(57.2%)(P<0.05); In the fourteams of coexpression of P-gp, CYP3A4, The chemotherapy ORR (90.5%) is thehighest in P-gp-/CYP3A4-team while the chemotherapy ORR rate is the lowest inP-gp+/CYP3A4+(31.3%), The diversity has statistical significance (P<0.05).5. The refractory rate is significantly higher in P-gp+team (65.0%) than that inP-gp-team (35.0%)(P<0.05); The refractory rate (60.0%) is significantly higher in CYP3A4+team than that in CYP3A4-team (24.0%)(P<0.05); the four team ofcoexpression of P-gp, CYP3A4, The refractory rate (68.8%) is the highest inP-gp-/CYP3A4-team while The refractory rate is the lowest in P-gp+/CYP3A4+(19.0%), The diversity has statistical significance (P<0.05).6. The result was attained by Kaplan-Meier survival curve analysis and log-ranktest. The overall survival of P-gp-team was longer than that of P-gp+team, Thediversity between the two teams has statistical significance (P=0.014); The overallsurvival of CYP3A4-team was longer than that of CYP3A4+team,, The diversitybetween the two teams has statistical significance (P=0.028).Conclusions：1．There is a higher expression of P-gp, CYP3A4in DLBCL tissues, which hintsthat there is a higher multidrug resistance phenomenon in these patients withoutchemotherapy.2. The expression of P-gp was closely related to Ann Arbor stage, extranodalinvolvement site in DLBCL tissues，and P-gp was found to be a valuable index todetermine the prognosis of DLBCL.3. P-gp and CYP3A4were important indicator to estimate Chemo-sensitivity inDLBCL, and there was synergistic effect between P-gp and CYP3A4on multidrugresistance in DLBCL. So detecting aggregated expression of the two proteins maybehave an important sense to select effective drug and set individualized chemotherapyregimens.4. Patients with positive expression of P-gp, CYP3A4have shorter OS and poorerprognosis than that with negative expression of P-gp, CYP3A4. these results suggest thatP-gp, CYP3A4may be useful markers of poor prognosis in DLBCL.