MiR-19a、miR-21和miR-29c在多发性骨髓瘤中的表达及临床意义  

Expressions of miR-19a, miR-21 and miR-29c in multiple myelomas and their clinical significances

作　　者：韩泽宇 张晓阳[1] 锁静 吕鸿雁[1] 藏美蓉 孙丽霞 张金巧[1] 宋晓宁[1] HAN Zeyu;ZHANG Xiaoyang;SUO Jing(Department of Hematology,the Third Hospital of Hebei Medical University,Hebei,Shijiazhuang 050000,China)

机构地区：[1]河北医科大学第三医院血液科,石家庄市050000

出　　处：《河北医药》2024年第24期3691-3696,共6页Hebei Medical Journal

基　　金：河北省医学科学研究课题(编号:20190072)。

摘　　要：目的探讨microRNA-19a(miR-19a)、microRNA-21(miR-21)和microRNA-29c(miR-29c)在多发性骨髓瘤(MM)中的相对表达水平及其对MM的临床意义。方法选取2022年5月至2023年7月初诊MM患者的28例作为MM组,另外纳入无恶性血液疾病的健康供者(healthy donor,HD)9例作为对照。采用RT-PCR方法检测骨髓血浆和外周血清中miR-19a、miR-21和miR-29c相对表达水平,通过受试者工作曲线分析3种miRNA的诊断价值。调查入选者的临床资料包括血红蛋白、血清白蛋白、球蛋白、β2-微球蛋白、血清钙、血肌酐、乳酸脱氢酶、M蛋白、血沉、超敏C-反应蛋白、淋巴细胞亚群及临床分期与3种miRNA进行相关性分析。结果MM组血清miR-19a、miR-21及miR-29c相对表达水平相对于HD组均低,而MM组骨髓miR-19a、miR-21及miR-29c表达水平相对于HD组均高,且MM组的骨髓表达水平比血清高(P<0.05)。在MM组血清中,miR-19a、miR-21和miR-29c与超敏C-反应蛋白水平皆呈负相关[(r=-0.6220,P=0.0201)、(r=-0.6659,P=0.0113)、(r=-0.5429,P=0.0479)];miR-21和miR-29c与球蛋白呈正相关[(r=0.5692,P=0.0366)、(r=0.5385,P=0.0500)],miR-21和miR-29c与M蛋白呈正相关[(r=0.5938,P=0.0282)、(r=0.5497,P=0.0449)]。除此之外,miR-21与淋巴细胞亚群的CD_(8)^(+)呈正相关性(r=0.6132,P=0.0224),与CD_(4)^(+)/CD_(8)^(+)呈负相关(r=-0.5780,P=0.0333),miR-29c与CD_(8)^(+)呈正相关(r=0.5516,P=0.0438)。受试者工作曲线分析血清miR-19a、miR-21及miR-29c的曲线下面积分别为0.8492、0.8889、0.8413,三者联合诊断MM的AUC为0.9683;骨髓miR-19a、miR-21及miR-29c的AUC分别为0.8788、0.8636、0.9091,无法计算骨髓中三者联合诊断MM的价值。结论初诊MM患者的miR-19a、miR-21及miR-29c在血清中皆呈低表达,而在骨髓中皆呈高表达,并且不论是在血清还是骨髓中这3个miRNA都可以很好地区分MM和HD,但是血清3个miRNA联合诊断MM更有价值,并且具有成为MM预后生物标志物和治疗靶点的潜力。Objective To investigate the expression levels of microRNA-19a(miR-19a),microRNA-21(miR-21),and microRNA-29c(miR-29c)in multiple myelomas(MM)and their clinical significances.Methods Between May 2022 and July 2023,28 patients initially diagnosed with MM were included in the MM group,while 9 healthy donors(HD)without malignant hematological diseases were included in the control group.Expression levels of miR-19a,miR-21,and miR-29c in bone marrow plasma and peripheral serum were detected in MM patients by reverse transcription-polymerase chain reaction(RT-PCR).The diagnostic value of the three miRNAs was analyzed using the receiver operating characteristic(ROC)curves.Correlations of hemoglobin,serum albumin,globulin,β2-microglobulin,serum calcium,serum creatinine,lactate dehydrogenase,M protein,erythrocyte sedimentation rate(ESR),hypersensitive C-reactive protein(hs-CRP),lymphocyte subsets,and clinical stages of MM with the three miRNAs were analyzed using Spearman's correlation.Results Serum miR-19a,miR-21,and miR-29c levels were significantly lower in the MM group than the HD group,while those in the bone marrow were significantly higher in the MM group(P<0.05).MiR-19a,miR-21 and miR-29c were all negatively correlated with hs-CRP levels(r=-0.6220,P=0.0201;r=-0.6659,P=0.0113;r=-0.5429,P=0.0479.There was a positive correlation of miR-21 and miR-29c with globulin(r=0.5692,P=0.0366;r=0.5385,P=0.0500),and a positive correlation of miR-21 and miR-29c with M protein(r=0.5938,P=0.0282;r=0.5497,P=0.0449).In addition,miR-21 was positively correlated with CD_(8)^(+) lymphocyte subsets(r=0.6132,P=0.0224)and negatively correlated with CD_(4)^(+)/CD_(8)^(+)(r=-0.5780,P=0.0333).MiR-29c was positively correlated with CD_(8)^(+)(r=0.5516,P=0.0438).ROC curve analysis showed that the area under the curve(AUC)of serum miR-19a,miR-21 and miR-29c was 0.8492,0.8889 and 0.8413,respectively,and the AUC of the three combined to diagnose MM was 0.9683.AUC of miR-19a,miR-21 and miR-29c in bone marrow was 0.8788,0.8636 and 0.9091,respectivel

关 键 词：多发性骨髓瘤 微小RNA-19a 微小RNA-21 微小RNA-29c 临床意义 

分 类 号：R733.3[医药卫生—肿瘤]