WDR19 expression is increased in prostate cancer compared with normal cells, but low-intensity expression in cancers is associated with shorter time to biochemical failures and local recurrence

被引:15
作者
Lin, Biaoyang [1 ,2 ,3 ]
Utleg, Angelita G. [3 ]
Gravdal, Karsten [5 ,6 ]
White, James T. [3 ]
Halvorsen, Ole J. [5 ,6 ]
Lu, Wei [3 ]
True, Lawrence D. [1 ]
Vessella, Robert [1 ]
Lange, Paul H. [1 ]
Nelson, Peter S. [4 ]
Hood, Leroy [3 ]
Kalland, Karl-Henning [5 ,6 ]
Akslen, Lars A. [5 ,6 ]
机构
[1] Univ Washington, Dept Urol, Seattle, WA 98195 USA
[2] Zhejiang Calif Int Nanosyst Inst, Hangzhou, Peoples R China
[3] Univ Washington, Inst Syst Biol, Seattle, WA 98195 USA
[4] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA
[5] Univ Bergen, Gade Inst, Dept Pathol, Sect Pathol, N-5021 Bergen, Norway
[6] Haukeland Hosp, N-5021 Bergen, Norway
关键词
D O I
10.1158/1078-0432.CCR-07-1535
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Purpose: Prostate cancer is the third leading cause of cancer death in the United States, following lung and colorectal cancer. We previously identified WDR19 as a prostate-specific, androgen-regulated gene. Here, we evaluate its utility as a prostate cancer tissue marker for diagnosis and prognostic evaluation. Experimental Design: Real-time quantitative PCR was done on a panel of prostate tissue isolated by laser capture microdissection. After generating antibodies against WDR19, tissue microarrays (TMA) were employed to compare WDR19 expression between normal, benign prostatic hyperplasia, and prostate cancer tissue. Results: Using microarrays and real-time quantitative PCR, we showed that WDR19 mRNA expression was increased in cancer. We further showed that WDR19 protein is localized to cytoplasmic subcellular granules and is expressed exclusively in prostate epithelia. Large-scale immunohistochemical staining using TMAs reveals a significant percentage of increase in intensely staining tissue cores in cancer tissue when compared with normal or benign prostatic hyperplastic tissue. Based on the analysis of a separate TMA for which clinical follow-up information was available, low-intensity WDR19 staining was significantly associated with decreased time to biochemical failure (P = 0.006) and with decreased time to locoregional recurrence (P = 0.050). Conclusions: WDR19 should be added to the list of prostate cancer tissue markers. The continued expansion of a multiple-marker panel will conceivably increase the sensitivity and specificity of prostate cancer diagnosis and prognosis.
引用
收藏
页码:1397 / 1406
页数:10
相关论文
共 39 条
[1]   Decoding cilia function: Defining specialized genes required for compartmentalized cilia biogenesis [J].
Avidor-Reiss, T ;
Maer, AM ;
Koundakjian, E ;
Polyanovsky, A ;
Keil, T ;
Subramaniam, S ;
Zuker, CS .
CELL, 2004, 117 (04) :527-539
[2]   A general approach to the generation of monoclonal antibodies against members of the tetraspanin superfamily using recombinant GST fusion proteins [J].
Azorsa, DO ;
Moog, S ;
Cazenave, JP ;
Lanza, F .
JOURNAL OF IMMUNOLOGICAL METHODS, 1999, 229 (1-2) :35-48
[3]  
Bouras T, 1999, J PATHOL, V188, P382, DOI 10.1002/(SICI)1096-9896(199908)188:4<382::AID-PATH365>3.0.CO
[4]  
2-O
[5]   Serum antibodies to huntingtin interacting protein-1: A new blood test for prostate cancer [J].
Bradley, SV ;
Oravecz-Wilson, KI ;
Bougeard, G ;
Mizukami, I ;
Li, L ;
Munaco, AJ ;
Sreekumar, A ;
Corradetti, MN ;
Chinnaiyan, AM ;
Sanda, MG ;
Ross, TS .
CANCER RESEARCH, 2005, 65 (10) :4126-4133
[6]   Discordant protein and mRNA expression in lung adenocarcinomas [J].
Chen, GA ;
Gharib, TG ;
Huang, CC ;
Taylor, JMG ;
Misek, DE ;
Kardia, SLR ;
Giordano, TJ ;
Iannettoni, MD ;
Orringer, MB ;
Hanash, SM ;
Beer, DG .
MOLECULAR & CELLULAR PROTEOMICS, 2002, 1 (04) :304-313
[7]  
CHINNAIYAN A, 2002, COMPLEXITY, V7, P22
[8]   Androgen axis in prostate cancer [J].
Culig, Zoran ;
Bartsch, Georg .
JOURNAL OF CELLULAR BIOCHEMISTRY, 2006, 99 (02) :373-381
[9]   Normalization of gene expression measurements in tumor tissues: comparison of 13 endogenous control genes [J].
de Kok, JB ;
Roelofs, RW ;
Giesendorf, BA ;
Pennings, JL ;
Waas, ET ;
Feuth, T ;
Swinkels, DW ;
Span, PN .
LABORATORY INVESTIGATION, 2005, 85 (01) :154-159
[10]   Delineation of prognostic biomarkers in prostate cancer [J].
Dhanasekaran, SM ;
Barrette, TR ;
Ghosh, D ;
Shah, R ;
Varambally, S ;
Kurachi, K ;
Pienta, KJ ;
Rubin, MA ;
Chinnaiyan, AM .
NATURE, 2001, 412 (6849) :822-826