Identification of a MicroRNA Panel for Clear-cell Kidney Cancer

被引:290
作者
Juan, David
Alexe, Gabriela
Antes, Travis
Liu, Huiqing
Madabhushi, Anant
Delisi, Charles
Ganesan, Shridhar
Bhanot, Gyan
Liou, Louis S. [1 ]
机构
[1] Boston Univ, Dept Pathol, Boston, MA 02118 USA
关键词
EXPRESSION PROFILES; GENES; SIGNATURE; HYPOXIA; REGIONS;
D O I
10.1016/j.urology.2009.10.033
中图分类号
R5 [内科学]; R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号
100201 [内科学]; 100221 [泌尿外科学];
摘要
OBJECTIVES To identify a robust panel of microRNA signatures that can classify tumor from normal kidney using microRNA expression levels. Mounting evidence suggests that microRNAs are key players in essential cellular processes and that their expression pattern can serve as diagnostic biomarkers for cancerous tissues. METHODS We selected 28 clear-cell type human renal cell carcinoma (ccRCC), samples from patient-matched specimens to perform high-throughput, quantitative real-time polymerase chain reaction analysis of microRNA expression levels. The data were subjected to rigorous statistical analyses and hierarchical clustering to produce a discrete set of microRNAs that can robustly distinguish ccRCC from their patient-matched normal kidney tissue samples with high confidence. RESULTS Thirty-five microRNAs were found that can robustly distinguish ccRCC from their patient-matched normal kidney tissue samples with high confidence. Among this set of 35 signature microRNAs, 26 were found to be consistently downregulated and 9 consistently upregulated in ccRCC relative to normal kidney samples. Two microRNAs, namely, MiR-155 and miR-21, commonly found to be upregulated in other cancers, and miR-210, induced by hypoxia, were also identified as overexpressed in ccRCC in our study. MicroRNAs identified as downregulated in our study can be correlated to common chromosome deletions in ccRCC. CONCLUSIONS Our analysis is a comprehensive, statistically relevant study that identifies the microRNAs dysregulated in ccRCC, which can serve as the basis of molecular markers for diagnosis. UROLOGY 75: 835-841, 2010. (C) 2010 Elsevier Inc.
引用
收藏
页码:835 / 841
页数:7
相关论文
共 25 条
[1]
MicroRNA functions in animal development and human disease [J].
Alvarez-Garcia, I ;
Miska, EA .
DEVELOPMENT, 2005, 132 (21) :4653-4662
[2]
CONTROLLING THE FALSE DISCOVERY RATE - A PRACTICAL AND POWERFUL APPROACH TO MULTIPLE TESTING [J].
BENJAMINI, Y ;
HOCHBERG, Y .
JOURNAL OF THE ROYAL STATISTICAL SOCIETY SERIES B-STATISTICAL METHODOLOGY, 1995, 57 (01) :289-300
[3]
Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers [J].
Calin, GA ;
Sevignani, C ;
Dan Dumitru, C ;
Hyslop, T ;
Noch, E ;
Yendamuri, S ;
Shimizu, M ;
Rattan, S ;
Bullrich, F ;
Negrini, M ;
Croce, CM .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2004, 101 (09) :2999-3004
[4]
MicroRNAs as oncogenes and tumor suppressors [J].
Chen, CZ .
NEW ENGLAND JOURNAL OF MEDICINE, 2005, 353 (17) :1768-1771
[5]
Implications of micro-RNA profiling for cancer diagnosis [J].
Cummins, J. M. ;
Velculescu, V. E. .
ONCOGENE, 2006, 25 (46) :6220-6227
[6]
MicroRNAs and the hallmarks of cancer [J].
Dalmay, T. ;
Edwards, D. R. .
ONCOGENE, 2006, 25 (46) :6170-6175
[7]
Identification of suitable endogenous control genes for microRNA gene expression analysis in human breast cancer [J].
Davoren, Pamela A. ;
McNeill, Roisin E. ;
Lowery, Aoife J. ;
Kerin, Michael J. ;
Miller, Nicola .
BMC MOLECULAR BIOLOGY, 2008, 9
[8]
Chromosomal deletions and tumor suppressor genes in prostate cancer [J].
Dong, JT .
CANCER AND METASTASIS REVIEWS, 2001, 20 (3-4) :173-193
[9]
The candidate tumor suppressor gene, RASSF1A, from human chromosome 3p21.3 is involved in kidney tumorigenesis [J].
Dreijerink, K ;
Braga, E ;
Kuzmin, I ;
Geil, L ;
Duh, FM ;
Angeloni, D ;
Zbar, B ;
Lerman, MI ;
Stanbridge, EJ ;
Minna, JD ;
Protopopov, A ;
Li, JF ;
Kashuba, V ;
Klein, G ;
Zabarovsky, ER .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2001, 98 (13) :7504-7509
[10]
Association of microRNA-34a overexpression with proliferation is cell type-dependent [J].
Dutta, Khokon Kumar ;
Zhong, Yi ;
Liu, Yu-Ting ;
Yamada, Takuji ;
Akatsuka, Shinya ;
Hu, Qian ;
Yoshihara, Minako ;
Ohara, Hiroki ;
Takehashi, Masanori ;
Shinohara, Takashi ;
Masutani, Hiroshi ;
Onuki, Janice ;
Toyokuni, Shinya .
CANCER SCIENCE, 2007, 98 (12) :1845-1852