Overexpression of EIF-5A2 is an independent predictor of outcome in patients of urothelial carcinoma of the bladder treated with radical cystectomy.
BACKGROUND
Our previous study has suggested an oncogenic role of eIF-5A2 in ovarian tumorigenesis. Abnormalities of eIF-5A2 and its clinical/prognostic significance, however, in urothelial carcinoma of the bladder (UC) are unclear.


METHODS
In this study, the methods of reverse transcription-PCR, immunohistochemistry, and fluorescence in situ hybridization were used to examine mRNA/protein expression and amplification of eIF-5A2 in a large cohort of UCs treated with radical cystectomy.


RESULTS
Up-regulated expression of eIF-5A2 mRNA was observed in 50% (8 of 16) of UCs, when compared with adjacent normal bladder tissues. Overexpression of EIF-5A2 protein and amplification of eIF-5A2 was examined informatively in 45.3% (39 of 86) and 10.6% (5 of 47) of UCs, respectively. In univariate survival analysis of the UC cohorts, a significant association of overexpression of EIF-5A2 with shortened patient survival (mean, 38.2 months versus 52.9 months, P = 0.001, log-rank test) was shown. In different subsets of UC patients, overexpression of EIF-5A2 was also a prognostic indicator in grade 1/2 (P = 0.0009) and grade 3 (P = 0.016) tumor patients, and in pT1 (P = 0.0089), pT2 (P = 0.0354), pT3/4 (P = 0.0058), pN0 (P = 0.0039), and pN1-2 (P = 0.0093) tumor patients. Importantly, EIF-5A2 expression (P = 0.0007) together with pT stage (P = 0.0001) provided significant independent prognostic variables in multivariate analysis.


CONCLUSIONS
These findings indicate that overexpression of EIF-5A2 in UCs is coincident with acquisition of a poor prognostic phenotype, suggesting that the expression of EIF-5A2, as detected by immunohistochemistry, is an independent molecular marker for shortened survival time of UC patients treated with radical cystectomy.
Chen
Wei
W
State Key Laboratory of Oncology in Southern China, Cancer Center, Sun Yat-Sen University, Guangzhou, China.
Luo
Jun-Hang
JH
Hua
Wen-Feng
WF
Zhou
Fang-Jian
FJ
Lin
Marie C
MC
Kung
Hsiang-Fu
HF
Zeng
Yi-Xin
YX
Guan
Xin-Yuan
XY
Xie
Dan
D
D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D016009:Chi-Square Distribution; D015653:Cystectomy / Q000379:methods*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D019394:Ki-67 Antigen / Q000096:biosynthesis; D008297:Male; D046228:Microarray Analysis; D008875:Middle Aged; D010448:Peptide Initiation Factors / Q000378:metabolism*; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016019:Survival Analysis; D015854:Up-Regulation; D001749:Urinary Bladder Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000601:surgery
D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D010448:Peptide Initiation Factors; C425967:eIF-5A2