Overexpression of EIF-5A2 Is an Independent Predictor of Outcome in Patients of Urothelial Carcinoma of the Bladder Treated with Radical Cystectomy
Overexpression of EIF-5A2 Is an Independent Predictor of Outcome in Patients of Urothelial Carcinoma of the Bladder Treated with Radical Cystectomy
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DOI：
10.1158/1055-9965.epi-08-0754
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发表时间：
2009-02-01
影响因子：
3.8
通讯作者：
Xie, Dan
中科院分区：
文献类型：
--
作者：
Chen, Wei;Luo, Jun-Hang;Xie, Dan
背景：我们先前的研究表明eIF-5A 2在卵巢肿瘤发生中的致癌作用。方法：采用逆转录聚合酶链反应（RT-PCR）、免疫组化和荧光原位杂交技术，检测膀胱尿路上皮癌（UC）中eIF-5A 2的mRNA/蛋白表达和扩增情况。结果：与癌旁正常膀胱组织相比，50%（8/16）的UC中eIF-5A 2 mRNA表达上调。分别在45.3%（86例中的39例）和10.6%（47例中的5例）的UC中检测到EIF-5A 2蛋白的过表达和eIF-5A 2的扩增。在UC队列的单变量生存分析中，显示EIF-5A 2过表达与缩短的患者生存期显著相关（平均38.2个月对52.9个月，P = 0.001，对数秩检验）。在不同亚组的UC患者中，EIF-5A 2的过表达也是1/2级UC患者的预后指标，（P = 0.0009）和3级pT 1（P = 0.0089）、pT 2（P = 0.0354）、pT 3/4（P = 0.0058）、pN 0（P = 0.0039）和pN 1 -2（P = 0.0093）肿瘤患者。重要的是，EIF-5A 2表达（P = 0.0007）与pT分期（P = 0.0001）在多变量分析中提供了显著的独立预后变量。这些发现表明，UC中EIF-5A 2的过表达与预后不良表型的获得相一致，表明EIF-5A 2的表达，如通过免疫组织化学检测的，是UC患者根治性化疗后生存时间缩短的独立分子标志物。（癌症流行病学生物标志物Prev 20091-18（2）：400-8）
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. (Cancer Epidemiol Biomarkers Prev 20091-18(2):400-8)