The Expression Of CyclinD1and Rb Protetn And E2F-1in Multiple Myeloma Biopsy And Its Clinical Significance

Background: Multiple myeloma (MM) belong to the blood systemtumors,and it’s a plasma cell malignant proliferative disease,and it accountsfor about10%of hematopoietic malignancies, and it’s pathogenesis isabnormal clonal proliferation of plasma cells in the bone marrow, secretion ofmonoclonal immunoglobulin or fragment thereof,which led to the organ ortissue damage.The main clinical manifestations have bone pain,renalinsufficiency,anemia and infection etc. In recent years,with the development ofdiagnostic techniques and the increasing aging population,it’s incidence isincreasing trend.The min method of treatment for the disease is chemotherapy,although proteasome inhibitors and other drugs to market significantlyimproved remission rates of MM and prolong the survival of patients,but thedisease is still incurable.Therefore,the study of the occurrence and thedevelopment mechanism of the disease have great significance.The evolution of the cell cycle is closely associated with tumor. Cellcycle disorders causing cells to unlimited independent division andproliferation,the tumor occur.The process of the cell cycle is adjusted by aseries of regulatory factors,among themin cluding positive regulatory factorsand negative regulatory factors.By affecting the process of the adjustmentfactor,and can regulate the cell cycle,and thus the unlimited autonomy divisionand proliferation of tumor cells can be suppressed.In-depth study the reason ofcell cycle disorder and the pathways and mechanisms of cell cycle regulatoryfactors,can provide new indicators and therapeutic targets for cancer diagnosisand treatment.Objective: By studying the expression and correlation of CyclinD1, Rbprotein and E2F-1protein in MM bone marrow biopsy and to explore theinfluence and mechanism of action in MM occurrence,development and prognosis.Methods: In this study, using immunohistochemical methods to detectthe expression of CyclinD1Rb and E2F-1three proteins in the bone marrowtissue of69cases MM patients and15cases dystrophic anemia patients.According to the clinical staging of ISS,69cases of MM bone marrow biopsyspecimens were divided into stage Ⅰ group (21cases),II stage group (20cases)and Phase III group (28cases),observe and analyse the expression of threeproteins in different stages of group and their relationship with diseases.According to the different types of detection of immunoglobulin,MM group isdivided into the IgG type (25cases),IgA type (19cases),light chain type (19cases) and the other type (6cases),observe and analyse the expression of threeproteins in the different sub-type group and their relationship with diseases.According to the remission after treatment,MM group were divided intocomplete remission group (CR group,38cases) and noncomplete remissiongroup (NR group,31cases),observe the expression of three proteins in thebone marrow biopsy specimens before and after treatment,and analyze therelationship between them and the prognosis of patients with MM.Results:1CyclinD1expression: In69patients with MM bone marrow biopsyspecimens,39cases were positive, the positive rate was56.52%,while in thecontrol group of15cases,2cases were positive, the positive rate was13.33%,compare the positive rate of two sets are significant differences(P<0.05), theexpression level of the control group was significantly lower than the MMgroup(P<0.05);In different stages of the MM group,the trend the positiveexpression rate and expression intensity of CyclinD1were increasing with thethe pathological stage increasing(P<0.05);In MM different sub-type group wasno significant difference(P>0.05);CyclinD1expression in MM beforetreatment,the positive rate and expression intensity of CyclinD1in the CRgroup and the NR group was no significant difference(P>0.05);After treatment,the positive rate and expression intensity of CyclinD1in the CR group wassignificantly lower than the NR group(P<0.05). 2Rb protein expression:In69patients with MM bone marrow biopsyspecimens,45cases were positive, the positive rate was65.22%,in the controlgroup of15cases,14cases were positive, the positive rate was93.33%,compare the positive rate of two sets are significant differences(P<0.05),theexpression level of the control group was significantly higher than the MMgroup(P<0.05);the trend of Rb protein positive rate and expression intensity inthe MM group from Ⅰs tage to Ⅲ stagewas gradually reduce(P<0.05);thepositive rate and expression intensity of Rb protein in the different MMsub-type group was no significant difference(P>0.05);before treatment thepositive rate and expression intensity of Rb protein in the the CR group wassignificantly higher than the NR group(P<0.05);after treatment positive rateand expression intensity in CR group was significantly higher than the NRgroup(P<0.05).3E2F-1protein expression:In69patients with MM bone marrow biopsyspecimens,52cases were positive,the positive rate was75.36%,in the controlgroup of15cases,5cases were positive,the positive rate was33.33%,there aresignificant differences in two groups,the positive rate and the expression levelof the the MM group were significantly higher than control group(P<0.05);during different pathological and different sub-type to compare the positiverate and the expression intensity were no significant difference(P>0.05);before treatment the positive rate and expression intensity of the CR group andthe NR group was no significant difference(P>0.05);after treatment thepositive rate and the expression intensity of the CR group was significantlylower than the NR group(P<0.05).4Correlation analysis:CyclinD1with Rb protein in MM bone marrowbiopsy was negatively correlated,CyclinD1with E2F-1was no significantcorrelation;Rb protein with E2F-1was negatively correlated.Conclusions:1CyclinD1was highly expressed in MM,the expression of strength andpositive rate have a growing trend with multiple myeloma disease stagingincreasing,and it can reflect the MM degree of progress. 2Rb protein showed low expression in MM patients, the trend is graduallydecreasing with the disease staging increasing, the NR group were higher thanthe CR group both before and after treatment,indicating that Rb has tosuppress the development and the occurrence of MM,it’s low expression andmissing were closely related to the occurrence of MM,and it can as theprognostic indicators of MM.3E2F-1was highly expressed in multiple myeloma group,and it hasnothing to do with the MM staging and typing,and it play a role in theoccurrence of the MM,and it can as a new diagnostic indicators.4CyclinD1and Rb protein in MM was a negative correlation,this is nosignificant correlation between CyclinD1and E2F-1,Rb protein wasnegatively correlated with E2F-1,The absence or low expression of Rb proteinleads to high expression of E2F-1.