Levels and clinical significance of serum microRNA-625 and microRNA-203 in patients with multiple myeloma
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摘要:目的
探讨多发性骨髓瘤(MM)患者血清微小RNA-625(miR-625)、血清微小RNA-203(miR-203)水平及临床意义。
方法选取2021年6月—2023年8月本院治疗的103例确诊MM患者为观察组，根据多发性骨髓瘤国际分期体系(ISS)分为Ⅰ期(n=23)、Ⅱ期(n=31)和Ⅲ期(n=49)。按照诊疗情况将患者分为初诊组(n=75)和复发组(n=28); 另选取103例同期本院体检健康者为对照组。采用逆转录-实时定量聚合酶链反应(RT-qPCR)法测定血清miR-625、miR-203水平; 采用多因素Logistic回归模型分析MM的影响因素; 采用受试者工作特征(ROC)曲线分析血清miR-625、miR-203对MM患者的诊断价值。
结果观察组M蛋白、血红蛋白、白蛋白、miR-625和miR-203水平均低于对照组，血肌酐、24 h尿蛋白、尿素氮、血清β2微球蛋白和血清钙水平高于对照组，差异有统计学意义(P < 0.05)。初诊组MM患者血清miR-625、miR-203水平均高于复发组，差异有统计学意义(P < 0.05)。Ⅱ期、Ⅲ期患者血清miR-625、miR-203水平均低于Ⅰ期患者, Ⅲ期患者血清miR-625、miR-203水平均低于Ⅱ期患者，差异有统计学意义(P < 0.05)。溶骨性病变 < 2个的MM患者血清miR-203水平低于溶骨性病变≥2个的患者，差异有统计学意义(P < 0.05); 骨病分级为1~2级的MM患者血清miR-625水平高于骨病分级为3~4级的患者，差异有统计学意义(P < 0.05)。miR-625、miR-203是MM发生的保护因素(P < 0.05)。血清miR-625、miR-203诊断MM的曲线下面积(AUC)分别为0.808、0.866, 二者联合诊断的AUC为0.919, 二者联合诊断优于血清miR-625、miR-203各自单独诊断(Z二者联合-miR-625=3.816、Z二者联合-miR-203=2.157, P=0.001、0.031)。
结论MM患者血清miR-625、miR-203水平下降，二者联合对MM具有较高的诊断价值。
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关键词:
- 多发性骨髓瘤 /
- 微小RNA-625 /
- 微小RNA-203 /
- 多发性骨髓瘤国际分期体系 /
- 肿瘤分期
Abstract:ObjectiveTo investigate the levels and clinical significance of serum microRNA-625 (miR-625) and serum microRNA-203 (miR-203) in patients with multiple myeloma (MM).
MethodsA total of 103 patients diagnosed as MM in the hospital from June 2021 to August 2023 were selected as observation group, and they were classified into stage Ⅰ (n=23), stage Ⅱ (n=31) and stage Ⅲ (n=49) according to the International Staging System (ISS) for multiple myeloma. The patients were divided into newly diagnosed group (n=75) and recurrent group (n=28) based on their diagnosis and treatment status. Additionally, 103 healthy individuals with physical examination in the hospital in the same period were selected as control group. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) was used to determine the levels of serum miR-625 and miR-203. A multivariate Logistic regression model was used to analyze the influencing factors of MM. The diagnostic value of serum miR-625 and miR-203 for MM patients was evaluated by receiver operating characteristic (ROC) curve.
ResultsThe levels of protein M, hemoglobin, albumin, miR-625 and miR-203 in the observation group were significantly lower than those in the control group, while the levels of serum creatinine, 24-hour urine protein, urea nitrogen, serum β2-microglobulin and serum calcium were significantly higher than those in the control group (P < 0.05). Serum levels of miR-625 and miR-203 in newly diagnosed MM group were significantly higher than those in the recurrent group (P < 0.05). The serum levels of miR-625 and miR-203 in patients with stage Ⅱ and Ⅲ were significantly lower than those in patients with stageⅠ, and the levels of miR-625 and miR-203 in patients with stage Ⅲ were significantly lower than those in patients with stage Ⅱ (P < 0.05). The serum miR-203 level in MM patients with osteolytic lesions less than 2 was significantly lower than that in patients with osteolytic lesions greater than or equal to 2 (P < 0.05). Serum miR-625 level in MM patients with grades 1 to 2 of bone disease was significantly higher than that in patients with grades 3 to 4 of bone disease (P < 0.05). The miR-625 and miR-203 were protective factors for the occurrence of MM (P < 0.05). The area under the curve (AUC) of serum miR-625 and miR-203 for diagnosing MM was 0.808 and 0.866 respectively, and the AUC of the combineddiagnosis of miR-625 and miR-203 was 0.919. The combined diagnosis of miR-625 and miR-203 was superior to the individual diagnosis of serum miR-625 and miR-203 (Zcombined-miR-625=3.816, Zcombined-miR-203=2.157, P=0.001, 0.031).
ConclusionSerum levels of miR-625 and miR-203 decrease in MM patients, and their combination has a high diagnostic value for MM.
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表 1 对照组、观察组血清miR-625、miR-203水平和临床资料比较(x±s)[n(%)]
临床病理特征 观察组(n=103) 对照组(n=103) t/χ2 P 性别 男 54(52.43) 48(46.60) 0.699 0.403 女 49(47.57) 55(53.40) 年龄 < 50岁 47(45.63) 51(49.51) 0.311 0.577 ≥50岁 56(54.37) 52(50.49) 体质量指数/(kg/m2) 23.16±3.24 22.94±3.38 0.477 0.634 血肌酐/(mg/dL) 1.86±0.33 0.87±0.21 25.687 < 0.001 24 h尿蛋白/mg 155.84±18.72 125.65±13.15 9.916 < 0.001 尿素氮/(mg/dL) 23.22±3.24 14.35±2.18 15.791 < 0.001 M蛋白/(g/L) 25.33±2.89 38.72±4.01 19.690 < 0.001 血红蛋白/(g/L) 92.50±10.72 115.43±12.65 9.950 < 0.001 血清β2微球蛋白/(mg/L) 4.62±1.02 1.36±0.19 21.135 < 0.001 白蛋白/(g/L) 31.54±4.25 48.36±5.38 17.731 < 0.001 血清钙/(mg/dL) 11.26±1.19 9.83±1.01 9.576 < 0.001 微小RNA-625 0.71±0.19 1.01±0.30 8.574 < 0.001 微小RNA-203 0.56±0.14 0.98±0.31 12.531 < 0.001 
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表 2 不同ISS分期患者血清miR-625、miR-203水平比较(x±s)
ISS分期 n 微小RNA-625 微小RNA-203 Ⅰ期 23 0.83±0.16 0.72±0.21 Ⅱ期 31 0.76±0.13* 0.59±0.15* Ⅲ期 49 0.63±0.09*# 0.47±0.11*# 与Ⅰ期比较, * P < 0.05; 与Ⅱ期比较, #P < 0.05。
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表 3 血清miR-625、miR-203表达与患者临床病理特征的关系(x±s)
临床病理特征 分类 n 微小RNA-625 微小RNA-203 性别 男 54 0.71±0.18 0.58±0.11 女 49 0.72±0.15 0.54±0.14 年龄 < 50岁 47 0.68±0.21 0.57±0.13 ≥50岁 56 0.74±0.19 0.56±0.08 血肌酐 < 2.00 mg/dL 42 0.73±0.21 0.58±0.15 ≥2.00 mg/dL 61 0.69±0.17 0.55±0.13 24 h尿蛋白 ≤150 mg 57 0.69±0.20 0.55±0.08 >150 mg 46 0.74±0.23 0.57±0.09 溶骨性病变 < 2个 65 0.72±0.12 0.59±0.09* ≥2个 38 0.70±0.16 0.51±0.12 骨病类型 骨质疏松 48 0.73±0.14 0.58±0.13 溶骨性破坏 27 0.69±0.17 0.57±0.14 病理性骨折 25 0.68±0.15 0.53±0.08 其他 3 0.66±0.11 0.51±0.09 骨病分级 1~2级 58 0.76±0.13# 0.58±0.11 3~4级 45 0.65±0.09 0.54±0.12 肿瘤细胞形态 成熟浆细胞 58 0.70±0.11 0.57±0.08 原幼浆细胞 45 0.73±0.09 0.54±0.10 ≥2个溶骨性病变比较, * P < 0.05;
与骨病分级1~2级比较, #P < 0.05。
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表 4 多因素Logistic分析MM发生的影响因素
影响因素 β SE Wald P OR 95%CI 血肌酐 0.226 0.246 0.847 0.357 1.254 0.774~2.031 微小RNA-625 -0.483 0.227 4.525 0.033 0.617 0.395~0.963 微小RNA-203 -0.627 0.261 5.778 0.016 0.534 0.320~0.891
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