尿液中的 microRNAs 作为多发性骨髓瘤的诊断生物标志物。

MicroRNAs in urine as diagnostic biomarkers for multiple myeloma.

机构信息

Clinical Laboratory Medicine, Beijing Shijitan Hospital, Capital Medical University, Beijing, China.

Beijing Key Laboratory of Urinary Cellular Molecular Diagnostics, Beijing, China.

出版信息

Int J Lab Hematol. 2021 Apr;43(2):227-234. doi: 10.1111/ijlh.13367. Epub 2020 Oct 17.

DOI:10.1111/ijlh.13367

PMID:33068078

Abstract

INTRODUCTION

Multiple myeloma (MM) is a hematological malignancy. It is of great clinical significance to screen microRNAs (miRNAs) in urine as noninvasive diagnostic biomarkers for MM.

METHODS

Urinary miRNAs in MM were performed by Agilent Bioanalyzer 2100 and verified by quantitative real-time PCR (qRT-PCR). Receiver operator characteristic (ROC) was used to evaluate the diagnostic value of abnormal miRNAs for MM. Progression-free survival (PFS) of MM was calculated by Kaplan-Meier.

RESULTS

In microarray analysis, twelve down-regulated miRNAs dysregulated in MM. The expression levels of miR-134-5p, miR-6500-5p, miR-548q, and miR-548y were validated. These miRNAs were significantly lower in MM (P < .05), but there was no significant difference between newly diagnosed, relapse, and remission group of MM (P> .05). ROC curve analysis showed that the sensitivity of miR-134-5p, miR-6500-5p, miR-548q, and miR-548y to MM was 91.7%, 100%, 100%, and 91.7%, and the specificity was 66.7%, 75.0%, 75.0%, and 100%, respectively. The four miRNAs were negatively correlated with the total urinary light chain (r = -0.427 P = .030, r = -0.461 P = .018, r = -0.469 P = .016, r = -0.493 P = .011). In addition, miR-134-5p, miR-6500-5p, and miR-548q were positively correlated with serum ALB (r = 0.518 P = .006, r = 0.400 P = .039,r = 0.492 P = .009). The expression level of miRNAs had no significant influence on PFS in MM patients (P> .05).

CONCLUSION

The results show that miR-134-5p, miR-6500-5p, miR-548q, and miR-548y are potential noninvasive diagnostic biomarkers for MM.

摘要

简介

多发性骨髓瘤（MM）是一种血液系统恶性肿瘤。筛选尿液中的微小 RNA（miRNA）作为 MM 的非侵入性诊断生物标志物具有重要的临床意义。

方法

采用 Agilent Bioanalyzer 2100 进行 MM 尿液中的 miRNA 分析，并通过实时定量 PCR（qRT-PCR）进行验证。采用受试者工作特征（ROC）曲线评估异常 miRNA 对 MM 的诊断价值。采用 Kaplan-Meier 计算 MM 的无进展生存期（PFS）。

结果

在微阵列分析中，有 12 个下调 miRNA 在 MM 中失调。验证了 miR-134-5p、miR-6500-5p、miR-548q 和 miR-548y 的表达水平。这些 miRNA 在 MM 中显著降低（P<0.05），但在初诊、复发和缓解组的 MM 之间无显著差异（P>0.05）。ROC 曲线分析表明，miR-134-5p、miR-6500-5p、miR-548q 和 miR-548y 对 MM 的敏感性分别为 91.7%、100%、100%和 91.7%，特异性分别为 66.7%、75.0%、75.0%和 100%。这四个 miRNA 与总尿轻链呈负相关（r=-0.427，P=0.030，r=-0.461，P=0.018，r=-0.469，P=0.016，r=-0.493，P=0.011）。此外，miR-134-5p、miR-6500-5p 和 miR-548q 与血清 ALB 呈正相关（r=0.518，P=0.006，r=0.400，P=0.039，r=0.492，P=0.009）。miRNA 的表达水平对 MM 患者的 PFS 无显著影响（P>0.05）。