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Clinical Chemistry and Laboratory Medicine (CCLM)

Published in Association with the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM)

Editor-in-Chief: Plebani, Mario

Ed. by Gillery, Philippe / Greaves, Ronda / Lackner, Karl J. / Lippi, Giuseppe / Melichar, Bohuslav / Payne, Deborah A. / Schlattmann, Peter

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Volume 55, Issue 5


Identification of a novel microRNA, miR-4449, as a potential blood based marker in multiple myeloma

Xianjuan Shen
  • Surgical Comprehensive Laboratory, Affiliated Hospital of Nantong University, Nantong, P.R. China
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Yan Ye / Jing Qi
  • Surgical Comprehensive Laboratory, Affiliated Hospital of Nantong University, Nantong, P.R. China
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Wei Shi
  • Surgical Comprehensive Laboratory, Affiliated Hospital of Nantong University, Nantong, P.R. China
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Xinhua Wu
  • Surgical Comprehensive Laboratory, Affiliated Hospital of Nantong University, Nantong, P.R. China
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Hongbing Ni / Hui Cong / Shaoqing Ju
  • Corresponding author
  • Laboratory Medicine Center, Affiliated Hospital of Nantong University, #20 Xisi Road, Nantong 226001, JS, P.R. China
  • Surgical Comprehensive Laboratory, Affiliated Hospital of Nantong University, Nantong, P.R. China, Phone/Fax: +86 0513 85052610
  • Email
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
Published Online: 2016-05-06 | DOI: https://doi.org/10.1515/cclm-2015-1108



miRNAs act in diverse biological processes including development, cell growth, apoptosis, and hematopoiesis, suggesting their role in cancer.


We examined the miRNAs perturbed in CD138+ primary multiple myeloma (MM) cells, using microarray analysis and real-time quantitative PCR (RT-qPCR). Serum miR-4449 expression levels were detected from 71 primary MM patients and 46 healthy controls by RT-qPCR.


Our analysis revealed up-regulation of 54 and down-regulation of 28 miRNAs in MM subjects compared to healthy controls. miR-4449 has not been reported in MM. It was found that the relative expression of bone marrow miR-4449 in MM patients (2.14±1.42) was higher than that in healthy controls (0.815±0.165) (U=8, p=0.0093). The relative expression of serum miR-4449 in MM patients (2.11±2.10) was significantly higher than that in healthy controls (0.357±0.235) (U=374, p<0.0001) and was significantly correlated with β2M, λ light and κ light chain concentration (r=0.480, p=0.0003; r=0.560, p<0.0001; r=0.560, p<0.0001), but not correlated with the lactate dehydrogenase (LDH) concentration (r=0.247, p=0.0611). The area under the curve (AUC) of the receiver-operating characteristics (ROC) curve of serum miR-4449 was 0.885 (95% CI, 0.826–0.945), which is higher than for other markers. Combining miR-4449, λ light chain, and β2M together, the sensitivity was highest compared with λ light chain or β2M alone, or combined.


The expression levels of serum miR-4449 in MM patients were significantly higher than in healthy controls, suggesting that it may prove to be useful in the auxiliary diagnosis of MM.

Keywords: auxiliary diagnosis; miR-4449; multiple myeloma; real-time quantitative PCR


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About the article

aXianjuan Shen and Yan Ye contributed equally as first authors.

Received: 2015-11-11

Accepted: 2016-04-04

Published Online: 2016-05-06

Published in Print: 2017-05-01

Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

Research funding: Grand support: the National Nature Science Foundation of China (81301498; 81271920; 81201351); Jiangsu Provincial Medical Innovation Team and Leading Talents (LJ201133); the Scientific Research Subject of Jiangsu Provincial Health Department (H201422; H201526); and translational medicine project of Affiliated Hospital of Nantong University (TDF-zh201407, TDF-zh201406).

Employment or leadership: None declared.

Honorarium: None declared.

Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

Citation Information: Clinical Chemistry and Laboratory Medicine (CCLM), Volume 55, Issue 5, Pages 748–754, ISSN (Online) 1437-4331, ISSN (Print) 1434-6621, DOI: https://doi.org/10.1515/cclm-2015-1108.

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