TY - JOUR
T1 - Utility of circulating cell-free RNA analysis for the characterization of global transcriptome profiles of multiple myeloma patients
AU - Chen, Maoshan
AU - Mithraprabhu, Sridurga
AU - Ramachandran, Malarmathy
AU - Choi, Kawa
AU - Khong, Tiffany
AU - Spencer, Andrew
PY - 2019/6/1
Y1 - 2019/6/1
N2 - 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.
AB - 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.
KW - Biomarker
KW - Circulating transcriptome
KW - Extracellular RNA
KW - Liquid biopsy
KW - Myeloma
KW - Non-coding RNA
KW - Relapse
UR - http://www.scopus.com/inward/record.url?scp=85073768403&partnerID=8YFLogxK
U2 - 10.3390/cancers11060887
DO - 10.3390/cancers11060887
M3 - Article
AN - SCOPUS:85073768403
SN - 2072-6694
VL - 11
JO - Cancers
JF - Cancers
IS - 6
M1 - 887
ER -