The Expression Of D-type Cyclins And P27Protein In Multiple Myeloma

Background： Multiple myeloma(MM)is a malignant disease byproliferation of monoclonal plasma cells in the bone marrow. It secretesmonoclonal immunoglobulins or their fragments and leads to injury at relevantorgan or tissue.The common clinical situation is bone pain, anemia, renalinsufficiency and infection. MM accounts for10%of malignant tumors ofhematopoietic system and there is a growth trend year by year. At presentchemotherapy have been mainly applied in clinical treatment, although newtherapeutic drugs such as proteasome inhibitor have been introduced andsurvival rates have improved, but MM is still remains incurable.The occurrence of tumor is caused by uncontrolled division or proliferationof normal cells and the ultimate pathway is the progression of cell cycle. Thisdiscovery indicates that alteration of cell cycle regulators,function will arrestthe cell cycle and the unlimited proliferation of tumor. Research into thefunction of cell cycle regulator may reveal new effective targets for genetherapy of malignant tumors.Objective:This study is to detect the expression of D-type cyclins(CyclinD1,CyclinD2and CyclinD3) and P27protein in multiple myelomaand their relationship, explore their function and mechanism in MMoccurrence,development and prognosis.Methods: Immunohistochemistry was used to detect the expression ofCyclinD1, CyclinD2, CyclinD3and P27in bone marrow tissues of10cases ofiron deficiency anemia patients and80cases of MM patients and theirrelationship. According to the difference of MM pathological staging,80casesof MM are divided into Ⅰperiod group,Ⅱperiod group and Ⅲperiod groupand observe the expression of four proteins in each group of MM and therelationship with the disease. According to the difference of immunoglobulin types,80cases of MM are divided into IgG group,IgA group,Light chaingroup and IgD group and observe the expression of four proteins in each groupof MM and the relationship with the disease.In the MM group, according tothe prognosis of MM,80cases of MM are divided into CR group and NRgroup and observe the expression of four proteins before and after treatment ofMM and the relationship with the prognosis of disease.Results:1. CyclinD1is low expression in control group. In10cases of controlgroup,1case is positive, the positive rate is10%.Over expression is seen inMM group. In80cases of MM group,46cases is positive, the positive rate is57.5%, which is significantly higher than control group(p＜0.05).In staginggroup of MM, with the increase of pathological grades, the expression andintensity of CyclinD1increased accordingly (p＜0.05).In type group ofMM,CyclinD1and disease classification have no obvious trend(p＞0.05).Inprognosis group of MM,before treatment: the expression and intensity ofCyclinD1have no obvious difference in CR group and NR group(p＜0.05).After treatment: the expression and intensity of CyclinD1in CR groupis significantly lower than NR group(p＜0.05).2. CyclinD2is not expressed in control group. The expression is seen inMM group. In80cases of MM group,31cases is positive, the positive rate is38.75%, which is significantly higher than control group(p＜0.05).Instaging group of MM, with the increase of pathological grades, the expressionand intensity of CyclinD2increased accordingly (p＜0.05).In type group ofMM,CyclinD2and disease classification have no obvious trend(p＞0.05).Inprognosis group of MM,before treatment: the expression and intensity ofCyclinD2have no obvious difference in CR group and NR group(p＜0.05).After treatment: the expression and intensity of CyclinD2in CR groupis significantly lower than NR group(p＜0.05).3. CyclinD3is not expressed in control group. Expression of cyclinD3isfound only in a small fraction of MM cases, but the expression and intensityare weak.12cases are positive in80cases of MM. Because the positive cases are less, there is no compared with each other in MM group.4. P27protein is expressed in control group. In10cases of control group,9cases is positive, the positive rate is90%.Low expression is seen in MMgroup. In80cases of MM group,30cases is positive, the positive rate is37.5%,which is significantly lower than control group(p＜0.05).In staging group ofMM, with the increase of pathological grades, the expression and intensity ofP27decreased accordingly (p＜0.05).In type group of MM,P27and diseaseclassification have no obvious trend(p＞0.05).In prognosis group ofMM,before treatment: the expression and intensity of P27have no obviousdifference in CR group and NR group(p＜0.05).After treatment: theexpression and intensity of P27in CR group is significantly lower than NRgroup(p＜0.05).5. Correlative investigation：The positive expression of CyclinD1orCyclinD2and P27in MM is negative correlation. The positive expression ofCyclinD3and P27in MM is positive correlation. While the three subtypes ofD-type cyclins is negative correlation between each other.Conclusion:1. CyclinD1and Cyclin2are over expression by one of two factors inhuman myeloma cells. One factor is high expression, the other must be lowexpression. There is a negative correlation between CyclinD1and CyclinD2.With the increase of pathological grades, their expression and intensityincreased accordingly. CyclinD1or Cyclin2is regulatory factor in malignanttransformation of MM and objectively reflect the progression of tumors andmalignant degree.2. Expression of cyclinD3is found only in a small fraction of MM cases,and the expression of the intensity is weak. CyclinD3is not obviousrelationship in the occurrence, development and malignant degree of MM.3. P27protein is expressed in control group. In MM group, it is lowexpression and with the increase of pathological grades, the expression andintensity of P27decreased accordingly. It is expressed on nucleus in controlgroup and CR group. P27protein can inhibit the growth of myeloma cell, and the different parts of its expression can be considered as an index ofprognostic evaluation.4. In the development of MM, P27negatively correlated with CyclinD1andCyclin2, positively with Cyclin3.While the three subtypes of D-type cyclins isnegative correlation between each other.