TY - JOUR
T1 - Metastasis suppressor gene Raf kinase inhibitor protein (RKIP) is a novel prognostic marker in prostate cancer
AU - Fu, Zheng
AU - Kitagawa, Yasuhide
AU - Shen, Ronglai
AU - Shah, Rajal
AU - Mehra, Rohit
AU - Rhodes, Daniel
AU - Keller, Peter J.
AU - Mizokami, Atsushi
AU - Dunn, Rodney
AU - Chinnaiyan, Arul M.
AU - Yao, Zhi
AU - Keller, Evan T.
PY - 2006/2/15
Y1 - 2006/2/15
N2 - 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.
AB - 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.
KW - Metastasis suppressor gene
KW - Prognostic marker
KW - Prostate cancer
KW - RKIP
KW - Tissue microarray
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U2 - 10.1002/pros.20319
DO - 10.1002/pros.20319
M3 - Article
C2 - 16175585
AN - SCOPUS:31944443578
SN - 0270-4137
VL - 66
SP - 248
EP - 256
JO - Prostate
JF - Prostate
IS - 3
ER -