Chen Maoshan, Mithraprabhu Sridurga, Ramachandran Malarmathy, Choi Kawa, Khong Tiffany, Spencer Andrew
Myeloma Research Group, Australian Centre for Blood Diseases (ACBD), Clinical Central School, Monash University, Melbourne 3004, Australia.
Malignant Haematology and Stem Cell Transplantation, Alfred Hospital, Melbourne 3004, Australia.
Cancers (Basel). 2019 Jun 25;11(6):887. doi: 10.3390/cancers11060887.
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.
在本研究中，我们评估了源自多发性骨髓瘤（MM）患者血浆的细胞外RNA（exRNA）用于全转录组表征的效用。对来自10名健康对照（HC）、5名新诊断（NDMM）以及12名复发难治（RRMM）MM患者的exRNA进行了分析和比较。我们发现约45%的exRNA基因是蛋白质编码基因，且所鉴定基因中约85%的覆盖率>70%。与HC相比，我们在MM患者中鉴定出632个差异表达基因（DEG），其中26个是NDMM和RRMM共有的。我们进一步分别鉴定出NDMM和RRMM特有的54个和191个基因，这些基因包括NDMM中的潜在生物标志物，如LINC00863、MIR6754、CHRNE、ITPKA和RGS18，以及RRMM中的LINC00462、PPBP、RPL5、IER3和MIR425，随后使用液滴数字PCR对其进行了验证。此外，在exRNA中鉴定出单核苷酸多态性和小插入缺失，包括在NDMM和RRMM之间表现出不同突变率的粘蛋白家族基因。这是血液系统恶性肿瘤中exRNA的首次全转录组研究，为利用exRNA增强我们对MM生物学的理解以及鉴定与MM患者诊断和预后相关的潜在生物标志物提供了依据。
