Whole transcriptome profiles of extracellular RNA of multiple myeloma patients

In this study, we evaluated the utility of extracellular RNA (exRNA) derived from the plasma of multiple myeloma (MM) patients for whole transcriptome characterization. exRNA from 10 healthy controls (HC), 5 newly diagnosed (NDMM) and 12 relapsed and/or refractory (RRMM) MM patients were analyzed and compared. We showed that ~45% of the exRNA genes were protein coding genes and ~85% of the identified genes were covered >70%. Compared to HC, we identified 632 differentially expressed genes (DEGs) in MM patients, of which 26 were common to NDMM and RRMM. We further identified 54 and 191 genes specific to NDMM and RRMM, respectively, and these included potential biomarkers such as LINC00863, MIR6754, CHRNE, ITPKA, RGS18 in NDMM and LINC00462, PPBP, RPL5, IER3, MIR425 in RRMM, that were subsequently validated using droplet digital PCR. Moreover, SNPs and small indels were identified in the exRNA, including mucin family genes that demonstrated different rates of mutations between NDMM and RRMM. This is the first transcriptome study of exRNA in a haematological malignancy and has provided the basis for the utilization of exRNA to enhance our understanding of the MM biology and to identify potential biomarkers relevant to the diagnosis and prognosis of MM patients.