循环 miRNA 作为多发性骨髓瘤和意义未明的单克隆丙种球蛋白血症的诊断生物标志物。
Circulating miRNAs as diagnostic biomarkers for multiple myeloma and monoclonal gammopathy of undetermined significance.
机构信息
Medical School of Chinese PLA & Medical Laboratory Center, The First Medical Center of Chinese PLA General Hospital, Beijing, China.
Clinical Laboratory Medicine, Beijing Shijitan Hospital, Capital Medical University, Beijing, China.
出版信息
J Clin Lab Anal. 2020 Jun;34(6):e23233. doi: 10.1002/jcla.23233. Epub 2020 Feb 10.
BACKGROUND
Multiple myeloma (MM) is still an incurable hematological malignancy evolved from asymptomatic monoclonal gammopathy of undetermined significance (MGUS). New evidence suggests that circulating microRNAs (miRNAs) can serve as stable diagnostic biomarkers for MM and MUGS.
METHODS
Serum miRNAs in MM patients, MUGS patients, and healthy controls (HC) were performed by Agilent Bioanalyzer 2100. MicroRNAs in MM detected as promising biomarkers were validated by using quantitative real-time PCR (qRT-PCR). Receiver operator characteristic (ROC) curve and multivariate logistic analysis were used to evaluate the diagnostic value of miRNAs for MM and MUGS.
RESULTS
In microarray analysis, the top ten differential expressed miRNAs in MM included miR-134-5p, miR-107, miR-15a-5p, miR-5159-3p, miR-1914-3p, miR-4723-3p, miR-5588-3p, miR-6893-3p, miR-7106-3p, and miR-6722-5p. Three up-regulated miRNAs (miR-134-5p, miR-107, and miR-15a-5p) were further validated. The elevated expression levels of miR-134-5p, miR-107, and miR-15a-5p in qRT-PCR were increased consistent with microarray analysis. These miRNAs distinguished MM and MUGS from HC significantly. Multivariate logistic analysis showed combination miR-107, miR-15a-5p with Hb, the AUC was 0.954 (95% CI: 0.890-1.000), sensitivity of 91.3%, and specificity of 93.7% for distinguishing MM from MUGS.
CONCLUSIONS
These data demonstrate that miR-134-5p, miR-107, and miR-15a-5p are potential diagnostic biomarkers in MM and MUGS. Moreover, the combination miR-107 and miR-15a-5p with Hb can distinguish MM from MUGS.
背景
多发性骨髓瘤（MM）仍然是一种无法治愈的血液恶性肿瘤，由无症状的单克隆丙种球蛋白血症（MGUS）演变而来。新的证据表明，循环 microRNAs（miRNAs）可以作为 MM 和 MUGS 的稳定诊断生物标志物。
方法
使用 Agilent Bioanalyzer 2100 对 MM 患者、MUGS 患者和健康对照（HC）的血清 miRNAs 进行分析。通过定量实时 PCR（qRT-PCR）验证作为有前途的 MM 和 MUGS 诊断生物标志物的 miRNAs。使用接收器操作特性（ROC）曲线和多变量逻辑分析评估 miRNAs 对 MM 和 MUGS 的诊断价值。
结果
在微阵列分析中，MM 中差异表达的前 10 个 miRNA 包括 miR-134-5p、miR-107、miR-15a-5p、miR-5159-3p、miR-1914-3p、miR-4723-3p、miR-5588-3p、miR-6893-3p、miR-7106-3p 和 miR-6722-5p。进一步验证了三个上调的 miRNA（miR-134-5p、miR-107 和 miR-15a-5p）。qRT-PCR 中 miR-134-5p、miR-107 和 miR-15a-5p 的表达水平升高与微阵列分析一致。这些 miRNA 可以显著区分 MM 和 MUGS 与 HC。多变量逻辑分析显示，miR-107、miR-15a-5p 与 Hb 联合，AUC 为 0.954（95%CI：0.890-1.000），对区分 MM 与 MUGS 的灵敏度为 91.3%，特异性为 93.7%。
结论
这些数据表明，miR-134-5p、miR-107 和 miR-15a-5p 是 MM 和 MUGS 的潜在诊断生物标志物。此外，miR-107 和 miR-15a-5p 与 Hb 的联合可以区分 MM 与 MUGS。
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