Expression of MAGE-A3, NY-ESO-1, LAGE-1 and PRAME in urothelial carcinoma.

Expression of MAGE-A3, NY-ESO-1, LAGE-1 and PRAME in urothelial carcinoma.
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DOI:
10.1038/bjc.2012.215
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发表时间:
2012-06-26
影响因子:
8.8
通讯作者:
Orntoft, T. F.
Orntoft, T. F.
中科院分区:
医学1区
文献类型:
--
作者:
Dyrskjot, L.;Zieger, K.;Lildal, T. Kissow;Reinert, T.;Gruselle, O.;Coche, T.;Borre, M.;Orntoft, T. F.

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癌症-睾丸(CT)抗原作为癌症患者免疫治疗靶点的潜力已被大量研究,目前正在进行基于CT抗原MAGE-A3和NY-ESO-1的癌症疫苗试验。我们使用特异性q-RT-PCR分析了一组膀胱肿瘤中CT基因MAGE-A3、NY-ESO-1(CTAG 1B)、拉格-1(CTAG 2)和PRAME的表达,这些膀胱肿瘤来自350例长期随访和详细治疗信息的患者。总体而言,43%的肿瘤表达MAGE-A3,35%表达NY-ESO-1,27%表达拉格-1,20%表达PRAME。总之,56%的肿瘤表达了至少一种分析的CT基因。非肌层浸润性肿瘤CT基因表达的单变量考克斯回归分析显示MAGE-A3(P=0.026)、拉格-1(P=0.001)和NY-ESO-1(P=0.040)的表达与较短的无进展生存期显著相关。此外,我们发现表达PRAME的肿瘤患者对化疗反应较差(P=0.02,χ2检验)。癌-睾丸基因经常在膀胱癌中表达,特别是在高阶段和高级别的肿瘤中。此外,CT基因表达可能具有预后和预测价值。针对膀胱癌中CT抗原的特异性免疫疗法的发展可能最终增加患者的存活率。
The potential for cancer-testis (CT) antigens as targets for immunotherapy in cancer patients has been heavily investigated, and currently cancer vaccine trials based on the CT antigens, MAGE-A3 and NY-ESO-1, are being carried out. We used specific q-RT-PCR assays to analyse the expression of the CT genes MAGE-A3, NY-ESO-1 (CTAG1B), LAGE-1 (CTAG2) and PRAME in a panel of bladder tumours from 350 patients with long-term follow-up and detailed treatment information. Overall, 43% of the tumours expressed MAGE-A3, 35% expressed NY-ESO-1, 27% expressed LAGE-1 and 20% expressed PRAME. In all, 56% of the tumours expressed at least one of the CT genes analysed. Univariate Cox regression analysis of CT gene expression in non-muscle-invasive tumours showed that expression of MAGE-A3 (P=0.026), LAGE-1 (P=0.001) and NY-ESO-1 (P=0.040) was significantly associated with a shorter progression-free survival. In addition, we found that patients with tumours expressing PRAME responded poorly to chemotherapy (P=0.02, χ2-test). Cancer-testis genes are frequently expressed in bladder cancer and especially in tumours of high stage and grade. In addition, the CT gene expression may have both prognostic and predictive value. Development of specific immunotherapy against the CT antigens in bladder cancer may ultimately increase patient survival.
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