| Objective:The purpose of this study was to detect the expression of monocarboxylic acid transporters 1/4(MCT1/4)in diffuse large B-cell lymphoma(DLBCL),and to study its relationship with clinical pathological data and survival.To explore the mechanism of PIK3 CA in DLBCL lactate transport.Methods:(1)Formalin-fixed and paraffinembedded DLBCL surgical samples were collected,and reactive hyperplasia was used as a control.The expression of MCT1/4 protein was detected by immunohistochemistry.(2)This study used BYL-719 to selectively inhibit the expression of PIK3 CA in DLBCL cell lines(NUDHL-1,OCI-LY8).Western blot was used to detect the changes of MCT1,MCT4,c-myc,LDHA,PD-L1.Real-time quantitative PCR was used to detect changes in MCT1/4 mRNA.The lactic acid LD kit measures intracellular lactate levels.Results:(1)MCT1 protein was highly expressed in non-GCB type(P=0.024).When MCT1 protein expression was high,DLBCL patients had poor sensitivity to the R-CHOP regimen(P=0.05).The expression of MCT4 protein was higher in non-GCB DLBCL(P=0.025),and the expression of MCT4 protein was statistically different from IPI>0(P=0.025)and LDH>240 U/L(P=0.05).Survival analysis showed no statistical difference between MCT1(P=0.208)and MCT4(P=0.273)protein expression with overall survival time.(2)In vitro,after inhibiting PIK3 CA expression,the levels of MCT1,MCT4 in protein(P<0.05)and mRNA(P<0.001)were lower than the control,and the expression of PD-L1,c-myc and LDHA proteins was lower than the blank group(P<0.05),the lactate levels in tumor cells increased(P<0.001).Conclusion:MCT1/4 protein can be expressed in DLBCL,which is related to tumor classification and regulation of lactate transport.PIK3 CA participates in the process of lactate transport in cells through MCT1/4.Therefore,we speculate that by inhibiting PIK3 CA,down-regulating MCT1/4 expression,regulating the process of lactate transport in DLBCL tumor cells,providing a new target for DLBCLtreatment. |
