Circulating serum microRNAs as novel diagnostic and prognostic biomarkers for multiple myeloma and monoclonal gammopathy of undetermined significance.
Multiple myeloma still remains incurable in the majority of cases prompting a further search for new and better prognostic markers. Emerging evidence has suggested that circulating microRNAs can serve as minimally invasive biomarkers for multiple myeloma and monoclonal gammopathy of undetermined significance. In this study, a global analysis of serum microRNAs by TaqMan Low Density Arrays was performed, followed by quantitative real-time PCR. The analyses revealed five deregulated microRNAs: miR-744, miR-130a, miR-34a, let-7d and let-7e in monoclonal gammopathy of undetermined significance, newly diagnosed and relapsed multiple myeloma when compared to healthy donors. Multivariate logistical regression analysis showed that a combination of miR-34a and let-7e can distinguish multiple myeloma from healthy donors with a sensitivity of 80.6% and a specificity of 86.7%, and monoclonal gammopathy of undetermined significance from healthy donors with a sensitivity of 91.1% and a specificity of 96.7%. Furthermore, lower levels of miR-744 and let-7e were associated with shorter overall survival and remission of myeloma patients. One-year mortality rates for miR-744 and let-7e were 41.9% and 34.6% for the 'low' expression and 3.3% and 3.9% for the 'high' expression groups, respectively. Median time of remission for both miR-744 and let-7e was approximately 11 months for the 'low' expression and approximately 47 months for the 'high' expression groups of myeloma patients These data demonstrate that expression patterns of circulating microRNAs are altered in multiple myeloma and monoclonal gammopathy of undetermined significance and miR-744 with let-7e are associated with survival of myeloma patients.
sevcik@med.muni.cz.
Lenka
L
Kubiczkova
Fedor
F
Kryukov
Ondrej
O
Slaby
Elena
E
Dementyeva
Jiri
J
Jarkovsky
Jana
J
Nekvindova
Lenka
L
Radova
Henrieta
H
Greslikova
Petr
P
Kuglik
Eva
E
Vetesnikova
Ludek
L
Pour
Zdenek
Z
Adam
Sabina
S
Sevcikova
Roman
R
Hajek
D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood / Q000235:genetics; D016022:Case-Control Studies; D002869:Chromosome Aberrations; D016000:Cluster Analysis; D018450:Disease Progression; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000097:blood / Q000235:genetics*; D008875:Middle Aged; D008998:Monoclonal Gammopathy of Undetermined Significance / Q000175:diagnosis* / Q000235:genetics* / Q000401:mortality; D009101:Multiple Myeloma / Q000175:diagnosis* / Q000235:genetics* / Q000401:mortality; D009367:Neoplasm Staging; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D012372:ROC Curve; D060888:Real-Time Polymerase Chain Reaction; D015203:Reproducibility of Results
D014408:Biomarkers, Tumor; D035683:MicroRNAs