Expression of X-linked inhibitor of apoptosis protein is a strong predictor of human prostate cancer recurrence

被引:70
作者
Seligson, David B.
Hongo, Fumiya
Huerta-Yepez, Sara
Mizutani, Yoichi
Miki, Tsuneharu
Yu, Hong
Horvath, Steve
Chia, David
Goodglick, Lee
Bonavida, Benjamin
机构
[1] Univ Calif Los Angeles, Dept Pathol & Lab Med, David Geffen Sch Med, Los Angeles, CA 90095 USA
[2] Univ Calif Los Angeles, Dept Biostat, David Geffen Sch Med, Los Angeles, CA 90095 USA
[3] Univ Calif Los Angeles, Dept Human Genet, David Geffen Sch Med, Los Angeles, CA 90095 USA
[4] Univ Calif Los Angeles, Dept Microbiol Mol Genet & Immunol, David Geffen Sch Med, Los Angeles, CA 90095 USA
[5] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, David Geffen Sch Med, Los Angeles, CA 90095 USA
[6] Kyoto Prefectural Univ Med, Kyoto Red Hosp 2, Dept Urol, Kyoto, Japan
[7] Hosp Infantil Mexico Dr Federico Gomez, Unidad Invest Enfermedades Oncol, Mexico City, DF, Mexico
关键词
D O I
10.1158/1078-0432.CCR-07-0960
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Purpose: The X-linked inhibitor of apoptosis protein (XIAP) is associated with cell survival by blocking caspase-mediated apoptosis.We examined the expression patterns of XIAP with regard to human prostate cancer, predicting that XIAP status may predict cancer recurrence and/or clinical outcome. Experimental Design: Immunohistochemistry was done on tissue microarrays constructed from 226 primary prostate cancer specimen. The protein expression distribution was examined across the spectrum of epithelial tissues and its association with standard clinicopathologic covariates and tumor recurrence was examined in 192 outcome-informative patients. Results: The mean XIAP expression was significantly higher in prostate cancer compared with prostatic intraepithelial neoplasia (PIN), normal, and benign prostatic hyperplasia. We observed that XIAP is an independent predictor of tumor recurrence in multivariate Cox proportional hazards analysis in all patients as well as after substratifying by Gleason score. Interestingly, patients with high XIAP levels had a much lower probability of tumor recurrence than those with lower XIAP expression. Even patients with high-grade tumors who had higher XIAP levels had a lower risk of recurrence compared with any patient whose tumors express lower XIAP. Conclusions: XIAP is expressed at higher levels in prostate cancers compared with matched normal tissues. High XIAP expression is strongly associated with a reduced risk of tumor recurrence and is not directly associated with Gleason score, tumor stage, capsular involvement, or preoperative prostate-specific antigen status, suggesting that it is a novel prognosticator and a potential target for prostate cancer diagnosis and therapy. Significantly, these findings provide important and extensive validation of previous results.
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页码:6056 / 6063
页数:8
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