Plasma extracellular RNA profiles in healthy and cancer patients. Sci Rep 2016 Jan 20;6:19413
Date
01/21/2016Pubmed ID
26786760Pubmed Central ID
PMC4726401DOI
10.1038/srep19413Scopus ID
2-s2.0-84955275191 (requires institutional sign-in at Scopus site) 245 CitationsAbstract
Extracellular vesicles are selectively enriched in RNA that has potential as disease biomarkers. To systemically characterize circulating extracellular RNA (exRNA) profiles, we performed RNA sequencing analysis on plasma extracellular vesicles derived from 50 healthy individuals and 142 cancer patients. Of ~12.6 million raw reads for each individual, the number of mappable reads aligned to RNA references was ~5.4 million including miRNAs (~40.4%), piwiRNAs (~40.0%), pseudo-genes (~3.7%), lncRNAs (~2.4%), tRNAs (~2.1%), and mRNAs (~2.1%). By expression stability testing, we identified a set of miRNAs showing relatively consistent expression, which may serve as reference control for exRNA quantification. By performing multivariate analysis of covariance, we identified significant associations of these exRNAs with age, sex and different types of cancers. In particular, down-regulation of miR-125a-5p and miR-1343-3p showed an association with all cancer types tested (false discovery rate <0.05). We developed multivariate statistical models to predict cancer status with an area under the curve from 0.68 to 0.92 depending cancer type and staging. This is the largest RNA-seq study to date for profiling exRNA species, which has not only provided a baseline reference profile for circulating exRNA, but also revealed a set of RNA candidates for reference controls and disease biomarkers.
Author List
Yuan T, Huang X, Woodcock M, Du M, Dittmar R, Wang Y, Tsai S, Kohli M, Boardman L, Patel T, Wang LMESH terms used to index this publication - Major topics in bold
AdolescentAdult
Aged
Aged, 80 and over
Biomarkers
Case-Control Studies
Female
Gene Expression Profiling
High-Throughput Nucleotide Sequencing
Humans
Male
MicroRNAs
Middle Aged
Neoplasm Staging
Neoplasms
RNA
RNA, Messenger
Sensitivity and Specificity
Young Adult