多发性骨髓瘤患者血清miR-1246和miR-4449的表达及临床意义

目的　探讨多发性骨髓瘤（multiple myeloma, MM）患者血清miR-1246 及miR-4449 的表达及其临床意义。方法　选取2017 年1 月~2020 年10 月涿州市医院收治的85 例MM 患者，依据国际分期系统分为I 期（n=17），II 期（n=27）和III 期（n=41），按照MM 的诊疗情况分为初诊组（n=68）和复发组（n=17）。另选取同期50 例正常者作为对照组。检测各组血清miR-1246，miR-4449 及β2- 微球蛋白（β2-MG）水平。应用受试者工作特征（ROC）曲线分析血清miR-1246，miR-4449 及β2-MG 水平诊断MM 的价值。结果　MM 组血清miR-1246（1.95±0.86），miR-4449（2.50±1.08）及β2-MG（6.30±2.42 mg/L）水平均明显高于对照组（0.42±0.07，0.73±0.16，1.85±0.64mg/L），差异有统计学意义（t=13.348, 14.365, 12.910, 均P<0.001）。MM 患者III 期血清miR-1246（3.05±1.37），miR-4449（3.96±1.87）及β2-MG（9.37±4.10 mg/L）水平均明显高于I 期（0.86±0.25，1.07±0.34，3.52±1.05mg/L）和II 期（1.84±0.81，2.28±1.05，5.40±1.61mg/L），差异有统计学意义（均P<0.001），且II 期血清miR-1246，miR-4449及β2-MG水平均明显高于I 期，差异有统计学意义（P<0.001）。复发组血清miR-1246（2.61±1.13），miR-4449（3.18±1.64）及β2-MG（8.04±3.27 mg/L）水平均明显高于初诊组(1.55±0.62, 1.92±0.95, 4.96±1.85mg/L)，差异均有统计学意义（t =10.217, 12.116, 8.530，均P<0.001）。ROC 曲线分析显示，miR-1246，miR-4449 及β2-MG 三项联合诊断MM 的曲线下面积（0.950，95%CI:0.887~0.995）最大，其灵敏度和特异度为98.2% 和85.0%。结论　MM 患者血清miR-1246及miR-4449 表达水平明显升高，且随着MM病情分期进展呈升高趋势，联合β2-MG检测有助于提高MM诊断的灵敏度。

Expression and Clinical Significance of Serum miR-1246 and miR-4449 in Patients with Multiple Myeloma

Objective　To investigate the expression and clinical significance of serum miR-1246 and miR-4449 in patients with multiple myeloma (MM). Methods　The 85 patients with MM admitted to Zhuozhou Hospital from January 2017 to July 2020 were divided into stage I (n=17), stage II (n=27) and stage III (n=41) according to the international staging system. According to the diagnosis and treatment of MM, they were divided into initial diagnosis group (n=68) and recurrence group (n=17). Another 50 normal persons in the same period were selected as the control group. The levels of serum miR-1246，miR-4449 and β2-MG were measured in each group. The diagnostic value of serum miR-1246，miR-4449 and β2-MG in MM were analyzed by ROC curve. Results　The levels of serum miR-1246（1.95±0.86）, miR-4449（2.50±1.08） and β2-MG（6.30±2.42 mg/L） in MM group were significantly higher than those in control group(0.42±0.07, 0.73±0.16, 1.85±0.64mg/L)，the differences were statistically significant（t=13.348, 14.365, 12.910, all P<0.001）.The levels of serum miR-1246（3.05±1.37）, miR-4449 （3.96±1.87） and β2-MG（9.37±4.10 mg/L）in MM patients at stage III were significantly higher than those at stage I(0.86±0.25, 1.07±0.34, 3.52±1.05mg/L) and II (1.84±0.81, 2.28±1.05, 5.40±1.61mg/L), the diffrences were statistically significant(P<0.001). The levels of serum miR-1246, miR-4449 and β2-MG in phase II were significantly higher than those in phase I, the differences were statistically significant (all P<0.001), respectively. The serum levels of miR-1246 (2.61±1.13), miR-4449 (3.18±1.64 ) and β2-MG (8.04±3.27 mg/L) in the recurrence group(1.55±0.62, 1.92±0.95, 4.96±1.85mg/L) were significantly higher than those in the initial diagnosis group, the differences were statistically significant (t=10.217,12.116,8.530，all P<0.001). ROC curve analysis showed that the area under the curve (0.950, 95%CI:0.887~0.995) of miR-1246，miR-4449 and β2-MG combined diagnosis MM was the largest, and its sensitivity and specificity were 98.2% and 85.0%, respectively. Conclusion　The levels of serum miR-1246 and miR-4449 in MM patients were significantly increased, and showed an upward trend with the progression of MM stage. The detection of miR-1246 and miR-4449 combined with β2- MG can improve the sensitivity of MM diagnosis.