| Objective:Multiple myeloma (Multiple myeloma, MM) belongs to theblood system malignant tumor, is the most common type of malignant plasmacell disease. the Malignant proliferation of Monoclonal plasma cell, andsecrete a lot of monoclonal immunoglobulin,Plasma cells in the normal pulpcloning and polyclonal immunoglobulin secretion is inhibited, the B-J proteinis excreted in the urine, often accompanied by extensive bone destruction,anemia, repeated infection, hyperviscosity syndrome,hypercalcemia, renalinsufficiency and so on a series of clinical manifestations, and will causeserious consequences and even death.The disease is mainly elderly people,men slightly more than women,the number of our patients in age of onset isabout53years old. In recent years,due to the increasing of medicalinstruments and diagnostic technology development and the aging of thepopulation rising, the incidence of multiple myeloma rate is on the rise. Thecause and pathogenesis of the disease are unclear.The treatment of this diseaseis chemotherapy, the median survival period is3-5years, with the applicationof proteasome inhibitors and other drugs, MM survival period is longer, butthe disease still can not be cured.Therefore, researching the occurrence and thedevelopment mechanism of multiple myeloma is very necessary.The eukaryotic cell proliferation is a sophisticated process,performed bythe cell cycle, there is a series of regulatory system which is consisted ofregulatory factor in cell, the orderly process of cell cycle is completed in aseries of intracellular regulatory factors, these factors ensure the precise ordercomplex cellular events,ensuring another event starts while one event iscompleted. Cell cycle driving mechanism and the monitoring mechanismform two major mechanism of cell cycle regulation. The driving mechanism isresponsible for the growth and proliferation of cells, including cyclin, cyclin dependent protein kinase and cancer protein; The monitoring mechanismprevent cell cycle operation when DNA is damaged or received cell growthinhibitory signal, and repair DNA,ensuring the complete of DNA replicationand caryomitosis, including cyclin dependent kinase inhibitor andanti-oncogene.The relationship between cell cycle regulation andtumorigenesis are very close, in a variety of carcinogenic factors, cell cycleregulatory factors occur mutation, amplification,deletion,ectopicchanges,causing the disorder of cell cycle, inactivation of monitoringmechanism, strengthen of driving mechanism, cells proliferate unlimited,eventually to form a tumor.It can provide a new monitoring index for tumordiagnosis, prognosis and provide a new target for tumor therapy by studyingthe regulation factors changes and the mechanism in the process of cell cycledisorder. The purpose of this study is to investigate the expression of pRb,E2F-1and P21in MM bone marrow biopsy and the effect of them on MMoccurrence,development.Methods:In this study, using immunohistochemical methods to detectthe expression of pRb, E2F-1and P21in medulla vivisect assay tissue of49cases MM patients and15cases dystrophic anemia patients. on the basis of theISS staging criteria,49cases of MM medulla vivisect assay tissue weredivided intoⅠ s tage group (13cases), II stage group (14cases) and III stagegroup (22cases), observe the expression of three proteins in different stages ofgroup and analyze their relationship with MM. according to the difference ofimmunoglobulin secretion types,49cases of MM bone marrow biopsyspecimens were divided into the IgG type (20cases),IgA type (10cases), lightchain type (10cases) and the other type (4cases), observe their expression inthe different sub-type group and analyze the relationship between them andMM.According to the remission after chemotherapy, MM group were dividedinto complete remission group (CR group,28cases) and no completelyremission group (NR group,21cases), observe the expression of threeproteins in the bone marrow biopsy specimens before and afterchemotherapy,and analyze the relationship between them and treatment outcomes of MM.Results:1pRb expression: There were39cases of positive expression in69patients with MM medulla vivisect assay tissue, the positive rate was79.59%,there were7cases of positive expression in15matched group with medullavivisect assay tissue, the positive rate was46.67%, there were obviousdifferences in two groups of positive expression rate (P<0.05), the MM groupwas higher than the matched group; there were differences between the twogroups in expression intensity(P<0.05), the MM group was stronger than thematched group.In different pathological stages, the positive expression ratefrom Ⅰg roup to III group were53.85%,78.56%,95.45%, the expression ratewas different in three groups (P<0.05),with increasing of pathologicalstaging,the positive rate showed an increasing trend; there were obviousdifferences in three groups in expression intensity(P<0.05), the expressionintensity from Ⅰg roup to III group showed an increasing trend. In differenttypes of group, the positive expression rate of pRb protein had no difference(P>0.05), the expression intensity was no difference too (P>0.05). Thepositive expression rate of two groups were difference before and aftertreatment (P<0.05), NR group was higher than CR group; the two groups aftertreatment were different in intensity of expression(P<0.05), NR group washigher than CR group, but there is no difference before treatment(P>0.05).2E2F-1expression: There were39cases of positive expression in49patients with MM medulla vivisect assay tissue,the positive rate was79.60%,and5cases of positive expression in15matched group with medulla vivisectassay tissue, the positive rate was33.33%, there were obvious differences intwo groups of positive expression rate (P<0.05), the MM group was higherthan matched group; there were differences between the two groups inexpression intensity(P<0.05), the MM group was stronger than the matchedgroup.In different stages, the positive expression rate from Ⅰ group toIII groupwere61.54%,71.43%,95.45%, the expression rate was different in threegroups (P<0.05), with increasing of pathological staging, E2F-1positive expression rate showed an increasing trend (P<0.05); there were obviousdifferences in the three groups in expression intensity(P<0.05), the expressionintensity from Ⅰg roup to III group showed an increasing trend. In differenttypes of group, the positive expression rate and expression intensity of E2F-1protein had no difference (P>0.05). before treatment, the expression intensityof two groups were difference(P<0.05), CR group was lower than NR group,the positive expression rate of the two groups were no significant difference(P>0.05); while after treatment, the positive expression rate and expressionintensity of two groups were difference(P<0.05), CR group was lower thanNR group (P<0.05).3P21expression: There were29cases of positive expression in49patients with MM medulla vivisect assay tissue, the positive rate was59.18%,and14cases of positive expression in15matched group with medulla vivisectassay tissue, the positive rate was93.33%, comparing the positive rate of twogroups had obvious difference (P<0.05), the MM group was lower than thematched group; there were differences between the two groups in expressionintensity(P<0.05), the matched group was stronger than the MM group. Indifferent stages, the positive expression rate from Ⅰ group toIII group were84.62%,64.29%,40.91%, the expression rate was different in three groups(P<0.05),with increasing of pathological staging, P21positive expression rateshowed an decreasing trend (P<0.05); there were obvious differences in thethree groups in expression intensity(P<0.05), the expression intensityfrom Ⅰg roup to III group showed an decreasing trend. In different types ofgroups,there were no significant difference in the positive expression rate andexpression intensity of P21(P>0.05). The positive expression rate of twogroups were difference before and after treatment (P<0.05), NR group waslower than CR group; there were no difference in the expression intensity oftwo groups neither before treatment nor after treatment(P>0.05).4Correlation analysis: pRb and P21protein in MM bone marrow biopsyshowed a negative correlation, the correlation between pRb and E2F-1ispositive; P21protein showed a negative correlation with E2F–1. Conclusion:1pRb protein showed high expression in MM patients, with increasing ofpathological staging, pRb positive rate and expression intensity showed anincreasing trend, the positive expression rate of NR group was significantlyhigher than those in CR group neither before treatment nor after treatment,there were no significant difference of the expression of pRb in different typesof groups.pRb may play a promoting function in the development of MM, theexpression level can reflect the progress of disease state.2E2F-1protein showed high expression in MM patients, with increasingof pathological staging, E2F-1positive expression rate and expressionintensity showed an increasing trend, and it has nothing to do with the MMtyping,after treatment, the expression of E2F-1in the CR group is lower thanin the NR group. E2F-1may play a promoting role in the development of MM,and can be used to evaluate the therapeutic effect and prognosis.3P21protein expression was low in the MM group, and with the stage ofdisease showed a decreasing trend, before and after treatment the CR groupwas higher than NR group, but no significant correlation with the type of MM.it is clear that P21plays an inhibitory role in the MM, can reflect the diseaseprognosis. |
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