RNA expression patterns in serum microvesicles from patients with glioblastoma multiforme and controls

被引:162
作者
Noerholm, Mikkel [1 ,2 ,3 ]
Balaj, Leonora [1 ,2 ]
Limperg, Tobias [1 ,2 ,4 ]
Salehi, Afshin [1 ,2 ,5 ]
Zhu, Lin Dan [1 ,2 ]
Hochberg, Fred H. [1 ,2 ]
Breakefield, Xandra O. [1 ,2 ]
Carter, Bob S. [1 ,2 ,5 ]
Skog, Johan [1 ,2 ,3 ]
机构
[1] Massachusetts Gen Hosp, Dept Neurol Neurosurg & Radiol, Boston, MA 02114 USA
[2] Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02114 USA
[3] Columbia Univ, Med Ctr, Exosome Diagnost Inc, New York, NY 10032 USA
[4] Univ Med Ctr Utrecht, Dept Neurosci & Pharmacol, Rudolf Magnus Inst Neurosci, Utrecht, Netherlands
[5] UCSD Sch Med, Div Neurol Surg, San Diego, CA 92103 USA
关键词
Exosomes; Microvesicles; Microarray; Biomarkers; Serum; Glioma; BLOOD; BIOMARKERS; EXOSOMES; CELLS; MICROARRAY; PROFILES; PROTEINS; VESICLES; INSIGHTS; GLIOMAS;
D O I
10.1186/1471-2407-12-22
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background: RNA from exosomes and other microvesicles contain transcripts of tumour origin. In this study we sought to identify biomarkers of glioblastoma multiforme in microvesicle RNA from serum of affected patients. Methods: Microvesicle RNA from serum from patients with de-novo primary glioblastoma multiforme (N = 9) and normal controls (N = 7) were analyzed by microarray analysis. Samples were collected according to protocols approved by the Institutional Review Board. Differential expressions were validated by qRT-PCR in a separate set of samples (N = 10 in both groups). Results: Expression profiles of microvesicle RNA correctly separated individuals in two groups by unsupervised clustering. The most significant differences pertained to down-regulated genes (121 genes > 2-fold down) in the glioblastoma multiforme patient microvesicle RNA, validated by qRT-PCR on several genes. Overall, yields of microvesicle RNA from patients was higher than from normal controls, but the additional RNA was primarily of size < 500 nt. Gene ontology of the down-regulated genes indicated these are coding for ribosomal proteins and genes related to ribosome production. Conclusions: Serum microvesicle RNA from patients with glioblastoma multiforme has significantly down-regulated levels of RNAs coding for ribosome production, compared to normal healthy controls, but a large overabundance of RNA of unknown origin with size < 500 nt.
引用
收藏
页数:11
相关论文
共 42 条
[11]  
Chen W, 1997, J PATHOL, V183, P345, DOI 10.1002/(SICI)1096-9896(199711)183:3<345::AID-PATH930>3.0.CO
[12]  
2-8
[13]   Comprehensive genomic characterization defines human glioblastoma genes and core pathways [J].
Chin, L. ;
Meyerson, M. ;
Aldape, K. ;
Bigner, D. ;
Mikkelsen, T. ;
VandenBerg, S. ;
Kahn, A. ;
Penny, R. ;
Ferguson, M. L. ;
Gerhard, D. S. ;
Getz, G. ;
Brennan, C. ;
Taylor, B. S. ;
Winckler, W. ;
Park, P. ;
Ladanyi, M. ;
Hoadley, K. A. ;
Verhaak, R. G. W. ;
Hayes, D. N. ;
Spellman, Paul T. ;
Absher, D. ;
Weir, B. A. ;
Ding, L. ;
Wheeler, D. ;
Lawrence, M. S. ;
Cibulskis, K. ;
Mardis, E. ;
Zhang, Jinghui ;
Wilson, R. K. ;
Donehower, L. ;
Wheeler, D. A. ;
Purdom, E. ;
Wallis, J. ;
Laird, P. W. ;
Herman, J. G. ;
Schuebel, K. E. ;
Weisenberger, D. J. ;
Baylin, S. B. ;
Schultz, N. ;
Yao, Jun ;
Wiedemeyer, R. ;
Weinstein, J. ;
Sander, C. ;
Gibbs, R. A. ;
Gray, J. ;
Kucherlapati, R. ;
Lander, E. S. ;
Myers, R. M. ;
Perou, C. M. ;
McLendon, Roger .
NATURE, 2008, 455 (7216) :1061-1068
[14]   Shedding microvesicles: artefacts no more [J].
Cocucci, Emanuele ;
Racchetti, Gabriella ;
Meldolesi, Jacopo .
TRENDS IN CELL BIOLOGY, 2009, 19 (02) :43-51
[15]   GLIOMAS - CLASSIFICATION WITH MR IMAGING [J].
DEAN, BL ;
DRAYER, BP ;
BIRD, CR ;
FLOM, RA ;
HODAK, JA ;
COONS, SW ;
CAREY, RG .
RADIOLOGY, 1990, 174 (02) :411-415
[16]   How large a training set is needed to develop a classifier for microarray data? [J].
Dobbin, Kevin K. ;
Zhao, Yingdong ;
Simon, Richard M. .
CLINICAL CANCER RESEARCH, 2008, 14 (01) :108-114
[17]  
Gnatenko Dmitri V., 2009, V496, P245, DOI 10.1007/978-1-59745-553-4_16
[18]  
Gomez GG, 2006, GENE THER MOL BIOL, V10A, P133
[19]   Retrotransposons revisited: The restraint and rehabilitation of parasites [J].
Goodier, John L. ;
Kazazian, Haig H., Jr. .
CELL, 2008, 135 (01) :23-35
[20]   Novel blood-based, five-gene biomarker set for the detection of colorectal cancer [J].
Han, Mark ;
Liew, Choong Tsek ;
Zhang, Hong Wei ;
Chao, Samuel ;
Zheng, Run ;
ThyeYip, Kok ;
Song, Zhen-Ya ;
Li, Hiu Ming ;
Geng, Xiao Ping ;
Zhu, Li Xin ;
Lin, Jian-Jiang ;
Marshall, K. Wayne ;
Liew, Choong Chin .
CLINICAL CANCER RESEARCH, 2008, 14 (02) :455-460