title: Identification of a novel microRNA, miR-4449, as a potential blood based marker in multiple myeloma.
abstract: BACKGROUND
  miRNAs act in diverse biological processes including development, cell growth, apoptosis, and hematopoiesis, suggesting their role in cancer.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Surgical Comprehensive Laboratory, Affiliated Hospital of Nantong University, Nantong, P.R.
authors.forename: Xianjuan
authors.initials: X
authors.lastname: Shen
authors.affiliation: Laboratory Medicine Center, Affiliated Hospital of Nantong University, Nantong, P.R.
authors.forename: Yan
authors.initials: Y
authors.lastname: Ye
authors.affiliation: Surgical Comprehensive Laboratory, Affiliated Hospital of Nantong University, Nantong, P.R.
authors.forename: Jing
authors.initials: J
authors.lastname: Qi
authors.affiliation: Surgical Comprehensive Laboratory, Affiliated Hospital of Nantong University, Nantong, P.R.
authors.forename: Wei
authors.initials: W
authors.lastname: Shi
authors.affiliation: Surgical Comprehensive Laboratory, Affiliated Hospital of Nantong University, Nantong, P.R.
authors.forename: Xinhua
authors.initials: X
authors.lastname: Wu
authors.affiliation: Laboratory Medicine Center, Affiliated Hospital of Nantong University, Nantong, P.R.
authors.forename: Hongbing
authors.initials: H
authors.lastname: Ni
authors.affiliation: Laboratory Medicine Center, Affiliated Hospital of Nantong University, Nantong, P.R.
authors.forename: Hui
authors.initials: H
authors.lastname: Cong
authors.affiliation: Laboratory Medicine Center, Affiliated Hospital of Nantong University, #20 Xisi Road, Nantong 226001, JS, P.R.
authors.forename: Shaoqing
authors.initials: S
authors.lastname: Ju
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood* / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007146:Immunoglobulin lambda-Chains / Q000097:blood; D008297:Male; D035683:MicroRNAs / Q000097:blood* / Q000235:genetics*; D008875:Middle Aged; D009101:Multiple Myeloma / Q000097:blood* / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; D007146:Immunoglobulin lambda-Chains; C000616964:MIRN-4449 microRNA, human; D035683:MicroRNAs
keywords: auxiliary diagnosis; miR-4449; multiple myeloma; real-time quantitative PCR