Metastasis suppressor gene Raf kinase inhibitor protein (RKIP) is a novel prognostic marker in prostate cancer

被引:159
作者
Fu, Z
Kitagawa, Y
Shen, RL
Shah, R
Mehra, R
Rhodes, D
Keller, PJ
Mizokami, A
Dunn, R
Chinnaiyan, AM
Yao, Z
Keller, ET
机构
[1] Univ Michigan, Dept Urol, Ann Arbor, MI 48109 USA
[2] Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA
[3] Kanazawa Univ, Dept Urol, Kanazawa, Ishikawa 920, Japan
[4] Tianjin Med Univ, Dept Immunol, Tianjin, Peoples R China
关键词
prognostic marker; RKIP; prostate cancer; metastasis suppressor gene; tissue microarray;
D O I
10.1002/pros.20319
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
BACKGROUND. Diminished expression of Raf kinase inhibitor protein (RKIP), an inhibitor of the Raf signaling cascade, promotes prostate cancer (PCa) metastasis in a murine model, suggesting that it is a metastasis suppressor gene. However, the prognostic significance of RKIP expression and its association with metastasis in PCa patients is unknown. METHODS. To investigate RKIP protein expression is a prognostic marker in PCa we performed immunohistochemical staining for RKIP expression in tissue microarrays consisting of 758 non-neoplastic prostate tissues, primary tumors and metastases from 134 PCa patients. The Cox proportional-hazards model was used to adjust for covariates including Gleason score, tumor volume, tumor weight, clinical stage, digital rectal exam findings, serum PSA level and surgical margins. RESULTS. RKIP expression was low in approximately 5%, 48%, and 89% of non-neoplastic prostate, primary tumors and metastases, respectively. Low RKIP expression in primary tumors was a strong positive predictive factor for PCa recurrence based on PSA levels. In patients whose primary tumors expressed high RKIP levels, the 7-year PSA recurrence rate was < 10%; whereas in patients with tumors with low RKIP expression the recurrence rate was 50% (P < 0.001). Multivariate analysis revealed RKIP was an independent prognostic factor (P < 0.001). CONCLUSION. In contrast to increased expression of pro-tumorigenic genes, these results demonstrate decreased protein expression of a gene, for example, RKIP, can serve as a prognostic marker in PCa patients.
引用
收藏
页码:248 / 256
页数:9
相关论文
共 46 条
[1]  
Ayala G, 2003, CLIN CANCER RES, V9, P4792
[2]  
Ayala G, 2003, CANCER RES, V63, P6244
[3]   Use of Gleason score, prostate specific antigen, seminal vesicle and margin status to predict biochemical failure after radical prostatectomy [J].
Blute, ML ;
Bergstralh, EJ ;
Iocca, A ;
Scherer, B ;
Zincke, H .
JOURNAL OF UROLOGY, 2001, 165 (01) :119-125
[4]   Prostate cancer involving the bladder neck: Recurrence-free survival and implications for AJCC staging modification [J].
Dash, A ;
Sanda, MG ;
Yu, MG ;
Taylor, JMG ;
Fecko, A ;
Rubin, MA .
UROLOGY, 2002, 60 (02) :276-280
[5]   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
[6]  
EPSTEIN JI, 1993, CANCER-AM CANCER SOC, V71, P3582, DOI 10.1002/1097-0142(19930601)71:11<3582::AID-CNCR2820711120>3.0.CO
[7]  
2-Y
[8]  
Etzioni R, 2002, J NATL CANCER I, V94, P981
[9]   Effects of Raf kinase inhibitor protein expression on suppression of prostate cancer metastasis [J].
Fu, Z ;
Smith, PC ;
Zhang, LZ ;
Rubin, MA ;
Dunn, RL ;
Yao, Z ;
Keller, ET .
JOURNAL OF THE NATIONAL CANCER INSTITUTE, 2003, 95 (12) :878-889
[10]   Osteoblasts produce soluble factors that induce a gene expression pattern in non-metastatic prostate cancer cells, similar to that found in bone metastatic prostate cancer cells [J].
Fu, Z ;
Dozmorov, IM ;
Keller, ET .
PROSTATE, 2002, 51 (01) :10-20