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


CONCLUSIONS
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.
Fu
Zheng
Z
Department of Urology, University of Michigan, Ann Arbor, Michigan 48109-0940, USA.
Kitagawa
Yasuhide
Y
Shen
Ronglai
R
Shah
Rajal
R
Mehra
Rohit
R
Rhodes
Daniel
D
Keller
Peter J
PJ
Mizokami
Atsushi
A
Dunn
Rodney
R
Chinnaiyan
Arul M
AM
Yao
Zhi
Z
Keller
Evan T
ET
D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics; D018572:Disease-Free Survival; D016147:Genes, Tumor Suppressor; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009362:Neoplasm Metastasis; D020411:Oligonucleotide Array Sequence Analysis; D049488:Phosphatidylethanolamine Binding Protein / Q000096:biosynthesis* / Q000235:genetics; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000097:blood / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
D014408:Biomarkers, Tumor; D049488:Phosphatidylethanolamine Binding Protein; D017430:Prostate-Specific Antigen