Identification of circulating microRNAs as diagnostic biomarkers for use in multiple myeloma

Abstract

Background:Multiple myeloma is a plasma cell disorder that is characterised by clonal proliferation of malignant plasma cells in the bone marrow, monoclonal paraprotein in the blood or urine and associated organ dysfunction. It accounts for approximately 1% of cancers and 13% of haematological cancers. Myeloma arises from an asymptomatic proliferation of monoclonal plasma cells termed monoclonal gammopathy of undetermined significance (MGUS).Methods:MicroRNA expression profiling of serum samples was performed on three patient groups as well as normal controls. Validation of the nine microRNAs detected as promising biomarkers was carried out using TaqMan quantitative reverse transcription PCR. MicroRNA levels in serum were normalised using standard curves to determine the numbers of microRNAs per μl of serum.Results:Three serum microRNAs, miR-720, miR-1308 and miR-1246, were found to have potential as diagnostic biomarkers in myeloma. Use of miR-720 and miR-1308 together provides a powerful diagnostic tool for distinguishing normal healthy controls, as well as patients with unrelated illnesses, from pre-cancerous myeloma and myeloma patients. In addition, the combination of miR-1246 and miR-1308 can distinguish MGUS from myeloma patients.Conclusion:We have developed a biomarker signature using microRNAs extracted from serum, which has potential as a diagnostic and prognostic tool for multiple myeloma.

WITHDRAWN: Expression profiles and biological implications of plasma miRNAs associated with chronic myeloid leukemia phases

“…A pooling strategy was conducted according to previously described recommendations [46]. Moreover, the pooling strategy to detect circulating miRNA profiles have been applied in a series of patients with multiple myeloma [46], acute myeloid leukemia [19] and breast cancer [47].…”

Circulating microRNA expressions can predict the outcome of lenalidomide plus low-dose dexamethasone treatment in patients with refractory/relapsed multiple myeloma

“…First, some well-known prognostic miRNA markers of MM [2][3][4][5]15 such as miR-19a were not identified. Since we focused on RRMMs with bortezomib failure and used the miRNA-array which contains just part (381 miRNAs) of the known human miRNAs, there is a possibility that some significant miRNA markers were missed.…”

MicroRNA theragnostics for the clinical management of multiple myeloma

“…Several studies have identified miRNAs that are deregulated during myelomagenesis, and subsequent studies have explored the role of miRNAs as diagnostics to detect disease or to monitor myeloma progression. [23][24][25][26][27][28][29][30][31] These studies have found that the vast majority of miRNAs that are aberrantly expressed in MM cells are upregulated compared with their expression in normal PCS. 23 A recent study compared miRNA expression profiles (miREP) of 52 newly diagnosed MM patients with that obtained from PCs of two healthy donors.…”

“…30,52 As miRNAs are freely circulating and highly stable within the bloodstream, there is great interest for their use as biomarkers. miRNAs represent an important new class of biomarkers whose concentration in blood may emulate tissue-and disease-specific expression profiles.…”

“…28 The miRNA-193b-365 cluster is overexpressed in MM and three miRNAs-720, 1308 and 1246-were significantly higher in PCs of myeloma patients than healthy controls. 29,30 A comprehensive miREP study compared PCs from normal donors, those with monoclonal gammopathy of unknown significance (MGUS), MM patients and MMCLs using a custommade microarray chip with qRT-PCR. 31 MGUS patients had a group of upregulated miRNAs with known oncogenic potential including miRNA-21 and the miRNA-106-25 cluster.…”