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Open AccessArticle

Utility of Circulating Cell-Free RNA Analysis for the Characterization of Global Transcriptome Profiles of Multiple Myeloma Patients

1
Myeloma Research Group, Australian Centre for Blood Diseases (ACBD), Clinical Central School, Monash University, Melbourne 3004, Australia
2
Malignant Haematology and Stem Cell Transplantation, Alfred Hospital, Melbourne 3004, Australia
*
Author to whom correspondence should be addressed.
These authors contribute equally to the work.
Cancers 2019, 11(6), 887; https://doi.org/10.3390/cancers11060887
Received: 9 May 2019 / Revised: 12 June 2019 / Accepted: 21 June 2019 / Published: 25 June 2019
(This article belongs to the Special Issue Liquid Biopsy for Cancer)
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Abstract

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), five newly diagnosed (NDMM), and 12 relapsed and 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, and RGS18 in NDMM, and LINC00462, PPBP, RPL5, IER3, and MIR425 in RRMM, that were subsequently validated using droplet digital PCR. Moreover, single nucleotide polymorphisms 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 whole transcriptome study of exRNA in hematological 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. View Full-Text
Keywords: myeloma; extracellular RNA; circulating transcriptome; relapse; liquid biopsy; biomarker; non-coding RNA myeloma; extracellular RNA; circulating transcriptome; relapse; liquid biopsy; biomarker; non-coding RNA
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Chen, M.; Mithraprabhu, S.; Ramachandran, M.; Choi, K.; Khong, T.; Spencer, A. Utility of Circulating Cell-Free RNA Analysis for the Characterization of Global Transcriptome Profiles of Multiple Myeloma Patients. Cancers 2019, 11, 887.

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