| Background and Objective:Multiple myeloma(MM)is the most common type of plasma cell diseases accounting for about 10% of hematological malignancies in elderly patients,but the exact etiology of MM remains unknown.MM is characterized by the infiltration and proliferation of monoclonal plasma cells in the bone marrow.The secretion and sediment of monoclonal immunoglobulin caused clinical symptoms including extensive bone destruction,anemia,renal insufficiency,repeated infections,hypercalcemia,hyperviscosity syndrome,amyloidosis,which could lead to undesirable consequences.In the past 10 years,with the development of new drugs and stem cell transplantation,the overall survival time and the life quality of patients with MM have been greatly improved,but MM still cannot be cured.MM is a highly heterogeneous disease,and the initial symptoms,clinical manifestations and survival time are significantly different.Using above indexes,individual treatment schemes and the clinical evaluation showed the clinical importance.Therefore,therapeutic schedule and prognostic evaluation becomes investigative emphasis and hot spot of MM.It has the important clinical significance for looking for the effective prognostic markers and new therapeutic targets for MM.Some studies have shown that epigenetics may affect the occurrence and development of the tumors.With further deep understanding of the ncRNA,researchers should pay more and more attentions to the important function of Long non-coding RNA.Long non-coding RNA(LncRNA)is a class of RNA molecules whose transcripts are longer than 200 nt,and it does not encode protein with lacking an open reading frame.But the functions of lncRNA exhibit a wide range of biological effects,including differentiation,development and carcinogenesis.We have already known that 1ncRNAs play a very important role in the development of cancer.But the relationship between the selected lncRNAs and multiple myeloma is still unknown.Methods: The bone marrow samples of multiple myeloma in this study were selected from the CHANGZHENG hospital for treatment of initial diagnosed multiple myeloma patients.We classify 120 MM cases of CD138-positive plasma cells to the experimental group,besides 10 cases of normal bone marrow plasma cells as the control group.The qRT-PCR method was used for detecting expressions level of CRNDE,PMS2P3 and LOC400657.Then the median expression level of the detective lncRNA was selected as the cut-off value,and multiple myeloma patients were divided into high and lowexpression levels of lncRNA groups.Each group has 60 patients with complete clinical and pathological data which were used to analyze the differences between the two groups on the aspect of age,sex,platelets,hemoglobin(HB),creatinine,calcium,LDH,β2-microglobulin and chromosome examination and so on.Patients receivedcombination chemotherapy with PAD(bortezomib + epirubicin + dexamethasone)at least 4courses,and thecurativeeffect was analyzed.We compare the progression free survival(PFS)and overall survival(OS)of the multiple myeloma patients in two groups to explorethe correlation between the expression levels of lncRNA and the prognosis of patients with multiple myeloma.After siRNA technology was used to knock down the expression levels of CRNDE in myeloma cell line RPMI-8226,U266.Then cell function including proliferation,apoptosis and cycle in CRNDE experimental study.Results:(1)We found the expression of the three objectives lncRNA CRNDE,PMS2P3 and LOC400657 in bone marrow samples of patients with multiple myeloma were up-regulated.Compared with normal control group,the relative expression of lg CRNDE was 2.432 ± 0.029 VS.0.144 ± 0.029 of normal control(p <0.01);the relative expression of lg PMS2P3 was2.135 ± 0.033 VS.0.169 ± 0.038 of normal control(p <0.01);the relative expression of lgLOC400657 was 2.410 ± 0.033 VS.control-0.027 ± 0.057(p <0.01).(2)Combination analysis of multiple myeloma patients with clinicopathological parameters showed that compared to patients with low expression in CRNDE,patients with high expression of CRNDE have differences inISS stage(p = 0.027),platelets(p = 0.032),p53 deletion(p = 0.032),13q14.3 deletion(p = 0.009)and 1q21 amplification(0.026);compared to patients with low expression in PMS2P3,patients with high expression of PMS2P3 have differences in lactate dehydrogenase(p = 0.043),p53 deletion(p = 0.032)and 13q14.3 deletion(p = 0.003);compared to patients with low expression in LOC400657,patients with high expression of LOC400657 have differences inβ2-MG(p = 0.036)and 13q14.3 deletion(p = 0.025).(3)Therapeutic effect analysis showed there is no significant correlation between the expression levels of CRNDE,PMS2P3 and LOC400657 in bone marrow samples of patients with multiple myeloma patients receiving two and four efficacy PAD regimen.(4)Analysis of prognostic factors showed thatcompared to the group of low expression of CRNDE,the PFS(p = 0.035)and OS(p = 0.030)of the group of high expression of CRNDE with multiple myeloma patients were poor.Multivariate analysis did not find the expression of CRNDE in the bone marrow can be selected as theOSindependent prognostic factor for patients with multiple myeloma(p = 0.140).(5)Theresults of cell function test showed after down-regulating CRNDE,myeloma cells can significantly inhibit the proliferation of cells,increase apoptosis,and can cause G0 / G1 cell cycle arrest.Conclusion The present study found that the expressive level of CRNDE,PMS2P3 and LOC400657 significantly increased in bone marrow samples from patients with multiple myeloma than in normal control,so it may be used as a potential molecular marker for multiple myeloma.Patients with multiple myeloma bone marrow samples of highly expressed CRNDE have shorter PFS and OS,but multivariate analysis did not find CRNDE as an independent risk factor for predicting prognosis.Experiments show CRNDE cell function plays the role of oncogenes in multiple myeloma. |
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