Circulating Serum MicroRNA-130a as a Novel Putative Marker of Extramedullary Myeloma

Abstract

Poor outcome of extramedullary disease in multiple myeloma patients and lack of outcome predictors prompt continued search for new markers of the disease. In this report, we show circulating microRNA distinguishing multiple myeloma patients with extramedullary disease from myeloma patients without such manifestation and from healthy donors. MicroRNA-130a was identified by TaqMan Low Density Arrays and verified by quantitative PCR on 144 serum samples (59 multiple myeloma, 55 myeloma with extramedullary disease, 30 healthy donors) in test and validation cohorts as being down-regulated in myeloma patients with extramedullary disease. Circulating microRNA-130a distinguished myeloma patients with extramedullary disease from healthy donors with specificity of 90.0% and sensitivity of 77.1%, patients with extramedullary disease from newly diagnosed multiple myeloma patients with specificity of 77.1% and sensitivity of 34.3% in the test cohort and with specificity of 91.7% and sensitivity of 30.0% in the validation cohort of patients. Circulating microRNA-130a in patients with extramedullary myeloma was associated with bone marrow plasma cells infiltration. Further, microRNA-130a was decreased in bone marrow plasma cells obtained from patients with extramedullary myeloma in comparison to bone marrow plasma cells of myeloma patients without such manifestation, but it was increased in tumor site plasma cells of patients with extramedullary disease compared to bone marrow plasma cells of such patients (p<0.0001). Together, our data suggest connection between lower level of microRNA-130a and extramedullary disease and prompt further work to evaluate this miRNA as a marker of extramedullary disease in multiple myeloma.

The Non-Coding RNA Landscape of Plasma Cell Dyscrasias

“…High serum levels of miR-16 and miR-25 positively correlated with better OS in MM patients, whereas high miR-25 correlated with better PFS [193]. Increased miR-483-5p levels were found in plasma of MM patients and associated with either PFS or ISS staging [194]; conversely, lower levels of circulating miR-130a were found in extramedullary myeloma (EMM) patients as compared with newly diagnosed and relapsed patients, and could discriminate EMM from MM patients or healthy donors [195].…”

Liquid Biopsies in Multiple Myeloma

“…Liquid biopsies represent one of the possible solutions for more comprehensive analysis of MM patients. Various targets, which can be analyzed in MM samples, include circulating tumor cells [19], cell-free DNA (cfDNA) [20], microRNA (miRNA) [21] and long non-coding RNA (lncRNA) molecules [22]. This review summarizes current knowledge of all aspects of liquid biopsies in MM.…”

“…From the cytogenetic point of view, MM may be divided into two groups: hyperdiploid and non-hyperdiploid. Hyperdiploid genome is mostly characterized by trisomies of odd chromosomes (3,5,7,9,11,15,19,21) and is connected to better prognosis [5], while non-hyperdiploid genome is characterized by monosomies of chromosomes 8,13,14,16,17 and 22 and recurrent chromosomal translocations involving the immunoglobulin heavy chain (IgH) locus at 14q32. In MM, the most frequent chromosomal translocations are t(11;14)(q13;q32) (15-20% of MM patients) and t(4;14)(p16;q32) (12-15% of MM patients).…”

Biomarkers in Immunoglobulin Light Chain Amyloidosis

“…Moreover, miRNA were described as important dia gnostic and prognostic markers in oncology, since their expression profiles were able to stratify patients and predict clinical outcome [10]. MiRNA were repeatedly proven to play an important role in the pathogenesis of MM, including different development stages from MGUS till extramedullary myeloma [11][12][13][14][15]. Never theless, there is a complete lack of knowledge about circulating miRNA in ALA.…”