Objective: To detect the expression of miR-221/222 in serum and plasma cells in patients with monoclonal gammopathy of undetermined significance(MGUS) and multiple myeloma(MM), and to explore the possibility of miR-221/222 as biomarkers in the diagnosis and prognosis predicting of MGUS and MM. Methods: Bone marrow and serum samples from 14 patients with newly diagnosed MGUS, 81 patients with newly diagnosed or relapsed MM and 10 controls were collected from Sir Run Run Shaw Hospital of Zhejiang University and Tongde Hospital of Zhejiang Province during January 2013 and December 2015. The expressions of miR-221/222 in serum and in sorted CD138 positive plasma cells were detected by qRT-PCR, and the relative expression of miR-221/222 (Δct) was compared between the groups. Serum levels of miR-221 before and after treatment were compared in both remission group (n=22) and refractory group (n=13) in MM patients, and its correlation with serum level of β2-MG was assessed using Pearson's correlation analysis. Results: Serum levels of miR-221/222 in MGUS and MM groups were significantly higher than those in control group (all P<0.01), while miR-221/222 levels in plasma cells were significantly lower in MGUS and MM groups than those in the control group (P<0.05 or<0.01). No significant difference in miR-221/222 levels in serum and plasma cells was observed between MGUS group and MM group (all P>0.05). There was no correlation between miR-221/222 levels in serum and plasma cells (r=0.024 and -0.127, all P>0.05), but miR-221 levels were correlated with miR-222 levels in both serum and plasma cells (r=0.534 and 0.552, all P<0.01). Receiver operating characteristic (ROC) curves showed that the areas under the curve (AUCs) of serum miR-221/222, plasma cell miR-221/222 in diagnosis of MGUS/MM were 0.968, 0.976, 0.801 and 0.727, respectively. There was no significant difference in serum level of miR-221 among MM patients with different paraprotein isotypes (P>0.05), but serum level of miR-221 in patients with relapsed MM was higher than that in patients with newly diagnosed MM (P<0.01). Compared with the patients with MGUS or MM stageⅠ and Ⅱ, patients with MM stage Ⅲ were of higher serum levels of miR-221 (P<0.01). Serum level of miR-221 decreased after chemotherapy in the remission group (U=51.5, P<0.01), but such decrease was not observed in the refractory group (U=67.5, P>0.05). Serum level of β2-MG was positively correlated with serum level of miR-221 (r=0.524, P<0.01). Conclusion: miR-221/222 in serum and plasma cells may be biomarkers for early diagnosis of MGUS, and are helpful for diagnosis and efficacy evaluation of MM.
目的: 探讨意义未明单克隆免疫球蛋白病（MGUS）、多发性骨髓瘤（MM）患者血清和浆细胞中微RNA-221（miR-221）和微RNA-222（miR-222）的表达水平及其作为MGUS、MM诊断和预测预后生物学指标的可能性。
方法: 收集2013年1月至2015年12月浙江大学医学院附属邵逸夫医院及浙江省立同德医院14例初诊MGUS患者、81例初诊及复发MM患者和10名健康对照者的血清及骨髓标本，其中骨髓标本用CD138磁珠分选浆细胞。用实时定量PCR检测血清和浆细胞中miR-221/222的表达量。采用Δct表示miR-221/222的相对表达量并比较组间差异。比较缓解组和难治组MM患者治疗前后血清miR-221表达水平的变化，并分析其与血清β 2微球蛋白的相关性。
结果: MGUS患者和MM患者血清miR-221/222的表达量均较对照组高（均 P < 0.01），而浆细胞miR-221/222的表达量均较对照组低（ P < 0.05或< 0.01）；MGUS与MM患者miR-221和miR-222表达量的差异在血清中或在浆细胞中均无统计学意义（均 P>0.05）。miR-221和miR-222表达量在血清与浆细胞之间无相关性（ r=0.024和-0.127，均 P>0.05）；而血清和浆细胞miR-221与miR-222表达量之间均具有相关性（ r=0.534和0.552，均 P < 0.01）。受试者工作特征（ROC）曲线显示血清miR-221/222和浆细胞miR-221/222诊断MGUS、MM的曲线下面积（AUC）分别为0.968和0.976、0.801和0.727。MM患者不同M-蛋白类型之间血清miR-221的表达量差异无统计学意义（ P>0.05）。复发患者血清miR-221的表达量高于初诊患者（ P < 0.01）。DS分期为Ⅲ期MM患者血清miR-221表达量高于MGUS及DS分期Ⅰ期和Ⅱ期MM患者（ P < 0.01）。缓解组治疗后血清miR-221表达量低于治疗前（ U=51.5， P < 0.01），而难治组治疗前后血清miR-221表达量差异无统计学意义（ U=67.5， P>0.05）。MM患者血清β 2微球蛋白水平与血清miR-221的表达量呈正相关（ r=0.524， P < 0.01）。
结论: 检测患者血清、浆细胞miR-221/222表达量有助于MGUS的早期诊断，也有助于MM的诊断及疗效观察。