| Objective:Multiple myeloma(MM)is a plasma cell malignant tumor.Its pathogenesis is the abnormal proliferation of plasma cells in the bone marrow and the secretion of large amounts of clonal immunoglobulin or its fragments,leading to different degrees of osteolytic lesions,hypercalcemia,anemia,renal damage and other end-organ damages.Since MM mostly occurs in elderly patients,and the aging trend of the population in our country is becoming more and more obvious,the incidence of MM in our country has increased.The existing methods for diagnosing MM mainly include bone marrow cytology,plasma immunoglobulin detection,and immunofixation electrophoresis.The most important methods are bone marrow aspiration and biopsy,which are invasive examinations.microribonucleotides(micro RNA,miRNA)in circulating plasma has the advantages of being easily detectable,stable in existence,and less painful to patients,and it is expected to become a biomarker for MM diagnosis.MiRNA is an endogenous non-coding ribonucleic acid composed of 19-22 nucleotides.In recent years,many studies have shown that there are abnormal expressions of miRNAs in a variety of blood system diseases,including multiple myeloma.Specifically,the abnormal expression of miRNAs is closely related to the occurrence,development and prognosis of MM.Thus,the purpose of this study is to detect the expression level of miRNAs in the plasma of MM patients,screen out meaningful miRNA molecules,and conduct correlation studies with existing clinical detection indicators,in an attempt to explore their diagnostic value in MM.Methods:We firstly checked the MM chip and sequencing data in the literature and database,to screen candidate miRNAs.Then,we collected samples from 90 patients with MM who were treated in the Department of Hematology of our hospital from September 2019 to December 2020 as the experimental group,including the newly diagnosed group(30 cases),remission group(30 cases),refractory group(30 cases).Meanwhile,40 normal people were collected as healthy control group.Fluorescence quantitative PCR technology was used to detect the expression level of miRNAs in the plasma of each group.Results:1.Review and screening results.By searching literature and databases,we selected four miRNAs as our candidate miRNA,including mi R-448,mi R-149-5p,mi R-455-3p,mi R-455-5p.2.Comparison of four miRNAs between healthy control group and newly diagnosed group.The relative expression level of miRNA-448 in the healthy control group was 1.06±0.40 fold,whereas in the newly diagnosed group was 2.23±1.07 fold.And there was statistical difference between the above two groups(P<0.05).However,there were no differences of miRNA-149-5p,miRNA-455-3p,miRNA-455-5p between the healthy control group(1.41±0.81 fold,1.64±1.29 fold,1.33±0.77 fold)and the newly diagnosed group(1.18±0.70 fold,1.29±1.01fold),1.29±0.90 fold).3.Comparison of the expression levels of miRNA-448 in the four research groups.The relative expression levels of miRNA-448 in the healthy control group,newly diagnosed group,remission group and refractory group were 1.06±0.40 fold,2.23±1.07 fold,1.07±0.69 fold and 2.59±1.39 fold,respectively.The relative expression of plasma miRNA-448 in the newly diagnosed group was significantly higher than that in the healthy control group and remission group,respectively(P<0.05).At the same time,miRNA-448 in the refractory group was significantly higher in comparison to the healthy control group and remission group,respectively(P<0.05).There was no statistical difference between the relative expression of plasma miRNA-448 in the remission group and healthy control group(P>0.05).Also,there was no significant difference of mi R-448 expression between the newly diagnosed group and refractory group(P>0.05).4.Analysis of sensitivity and specificity of miRNA-448 as a diagnostic marker.The area under the ROC curve(AUC)of miRNA-448 in the newly diagnosed group was 0.888,and the 95% confidence interval was 0.812-0.963.When the expression level of plasma mi R-448 in patients with multiple myeloma is 1.455,the sensitivity for the diagnosis of multiple myeloma is 76.70%and the specificity is 87.50%,respectively.5.Correlation analysis of miRNA-448The expression level of plasma miRNA-448 in the newly diagnosed MM group was positively correlated with the proportion of plasma cells in the bone marrow(r=0.634,P<0.05),as well as the serum M protein content(r=0.443,P<0.05).However,the miRNA-448 expression in plasma was negatively correlated with the content of hemoglobin(r=-0.544,P<0.05).Conclusion:1.The expression level of mi R-448 in plasma in newly diagnosed MM patients and refractory MM patients is higher than that of normal people,respectively,while no difference was found between the remission group and healthy control group.2.The expression of mi R-448 in the plasma of newly diagnosed MM patients is positively correlated with the ratio of plasma cells in bone marrow and the content of M protein in serum,while negatively correlated with the content of hemoglobin.Therefore,mi R-448 may serve as a new biomarker for the diagnosis of MM and a potential molecular for the assessment of MM progression. |
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