Circulating miRNAs as diagnostic biomarkers for multiple myeloma and monoclonal gammopathy of undetermined significance

Abstract

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.

Potential diagnostic value of circulating miRNA for multiple myeloma: A meta-analysis

“… Author Year Country microRNAs Regulation mode Sample size Speci-men Diagnostic power MM Healthy Sen (%) Spe (%) AUC Single miRNA Kubiczkova, L. [23] 2014 Czech Republic let-7d Downregulated 103 30 Serum 0.641 0.867 0.804 Kubiczkova, L. [23] 2014 Czech Republic let-7e Downregulated 103 30 Serum 0.888 0.633 0.829 Li, J. [24] 2020 China miR-15a-5p Upregulated 23 18 Serum 0.870 0.610 0.804 Li, F. [25] 2015 China miR-16–1 Downregulated 90 19 Plasma 1.000 0.730 0.864 Hao, M. [26] 2015 China miR-19a Upregulated 108 56 Serum 0.773 0.897 0.910 Qiu, X. Y. [27] 2013 China miR-20a Downregulated 40 20 Plasma …”

“… [30] 2018 China miR-125b-5p Upregulated 35 20 Plasma 0.860 0.960 0.954 Kubiczkova, L. [23] 2014 Czech Republic miR-130a Downregulated 103 30 Serum 0.575 0.900 0.722 Li, J. [24] 2020 China miR-134-5p Upregulated 23 18 Serum 0.870 0.667 0.812 Hao, M. [26] 2015 China miR-135b-5p Upregulated 108 56 Serum 0.667 0.833 0.810 Nidhi Gupta. [21] 2019 Germany miR-143 Upregulated 30 30 Serum 0.767 0.767 0.854 Nidhi Gupta.…”

“…With the rise of miRNAs in recent years, many studies have shown that the accuracy of circulating miRNAs in the early diagnosis of MM is satisfactory but inconsistent[ [18] , [19] , [20] ]. This may be caused by factors such as different detection technologies, platforms, standards, and insufficient clinical samples.…”

MicroRNAs in urine as diagnostic biomarkers for multiple myeloma

“…Agilent Human, Release 21 (8*60K, Design ID: 070156) was used to analyze miRNA expression in MM and HC group. The samples labeling, hybridization, washing, and data analysis steps were completed according to the previous research 11 …”

Potential Diagnostic Value of Circulating miRNA for Multiple Myeloma: A Meta-Analysis.

“…With the rise of miRNAs in recent years, many studies have shown that the accuracy of circulating miRNAs in the early diagnosis of MM is satisfactory but inconsistent [18][19][20][21] . This may be caused by factors such as different detection technologies, platforms, standards, and insu cient clinical samples.…”