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

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 RT-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 miRNA-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 precancerous 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.