Overexpression of EIF-5A2 predicts tumor recurrence and progression in pTa/pT1 urothelial carcinoma of the bladder
Overexpression of EIF-5A2 predicts tumor recurrence and progression in pTa/pT1 urothelial carcinoma of the bladder
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DOI：
10.1111/j.1349-7006.2009.01126.x
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发表时间：
2009-05-01
期刊：
影响因子：
5.7
通讯作者：
Xie, Dan
中科院分区：
文献类型：
--
作者：
Luo, Jun-Hang;Hua, Wen-Feng;Xie, Dan
作者探讨了eIF-5A2基因在浅表性（pTa/pT1）尿路上皮癌（UC）中的异常状况，以及其与临床病理变量和患者预后的关系。采用免疫组织化学（IHC）、荧光原位杂交（FISH）、逆转录聚合酶链反应（RT-PCR）和western blotting等方法检测eIF-5A2蛋白/mRNA（信使RNA）在pTa/pT1 UCs中的表达和扩增情况。IHC检测38/112例（33.9%）pTa/pT1 UCs中EIF-5A2过表达。研究证实，过表达EIF-5A2与缩短UC患者无复发生存期（P = 0.002）以及缩短无进展生存期（P = 0.004）存在显著关联。重要的是，多因素Cox回归分析显示，EIF-5A2表达在肿瘤复发（P = 0.002）或肿瘤进展（P = 0.007）中都是一个重要的独立预后参数。FISH结果显示，在5/59的信息性UCs中检测到eIF-5A2扩增；在5例eIF-5A2扩增病例中，均观察到eIF-5A2过表达。在其余54例无eIF-5A2扩增的UCs中，16例也观察到eIF-5A2过表达。在13对UC及邻近正常组织中，8对UC通过RT-PCR检测到eIF-5A2 mRNA表达上调，而Western blotting仅在4/8对UC中检测到eIF-5A2蛋白表达升高。上述结果提示，免疫组化检测的EIF-5A2过表达可能预测pTa/pT1 UC患者的肿瘤复发和进展，EIF-5A2的蛋白表达可能不仅受基因扩增的调控，还受其他分子机制的调控。[j] .癌症科学2009；100:896-902。
The authors investigated the status of abnormalities of eIF-5A2 gene in superficial (pTa/pT1) urothelial carcinoma of the bladder (UC), as well as its correlation with clinicopathologic variables and patient outcome. The methods of immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), reverse transcription-polymerase chain reaction (RT-PCR) and Wetern blotting were utilized to examine protein/mRNA(messenger RNA) expression and amplification of eIF-5A2 in a cohort of pTa/pT1 UCs. Overexpression of EIF-5A2 was examined by IHC in 38/112 (33.9%) pTa/pT1 UCs. A significant association of overexpression of EIF-5A2 with shortened UC patient recurrence-free survival (P = 0.002), as well as with shortened progression-free survival (P = 0.004), was demonstrated. Importantly, multivariate Cox regression analysis revealed that EIF-5A2 expression provided a significant independent prognostic parameter either in tumor recurrence (P = 0.002) or in tumor progression (P = 0.007). FISH results demonstrated that eIF-5A2 amplification was detected in 5/59 of the informative UCs; in each of the five cases with eIF-5A2 amplification, overexpression of EIF-5A2 was observed. In the remaining 54 UCs without eIF-5A2 amplification, 16 cases were also observed to have overexpression of EIF-5A2. In 13 pairs of UC and adjacent normal tissues, eight UCs were examined and showed up-regulated eIF-5A2 mRNA by RT-PCR, while increased expression of EIF-5A2 protein was only detected in 4/8 UCs by Western blotting. These findings suggest that overexpression of EIF-5A2, as detected by IHC, may predict tumor recurrence and progression in pTa/pT1 UC patients, and the protein expression of eIF-5A2 might be regulated not only by gene amplification, but also by other molecular mechanisms. (Cancer Sci 2009; 100: 896-902).