Identification of a claudin-4 and E-cadherin score to predict prognosis in breast cancer
Identification of a claudin-4 and E-cadherin score to predict prognosis in breast cancer
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DOI：
10.1111/j.1349-7006.2011.02085.x
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发表时间：
2011-12-01
期刊：
影响因子：
5.7
通讯作者：
Kulka, Janina
中科院分区：
文献类型：
--
作者：
Szasz, Attila M.;Nemeth, Zsuzsanna;Kulka, Janina
claudins（CLDN）和E-cadherin（CDH-1）的表达升高与预后不良相关。我们的目的是进行全面的分析，以评估其预测乳腺癌预后的潜力。在包含1809名乳腺癌患者的表达测量的数据集中，评估了mRNA水平的CLDN-1、CLDN-35、CLDN-7、CLDN-8、CLDN-10、CLDN-15、CLDN-18和E-cadherin的表达与生存率的相关性。应用组织芯片技术和免疫组化方法检测197例乳腺癌组织中CLDN-15、CLDN-7和E-cadherin蛋白的表达。使用387例患者的额外验证集来测试所得预后评分的准确性。基于对公开数据集的生物信息学筛选，CLDN-3、CLDN-4、CLDN-7和E-cadherin的元基因显示在生存分析中具有最强的预测能力。由CLDN-2、CLDN-4和E-cadherin组成的免疫组化蛋白质谱能够以训练集中最有效的方式预测结果。结合上述两种方法的重叠成员产生了claudin-4和E-cadherin评分（CURIO），其能够准确预测验证队列中的无复发生存期（P = 0.029）。包括临床病理变量和CURIO在内的多因素分析显示，CURIO保持其预测能力（P = 0.040）。此外，CURIO能够进一步改善预后，将管腔A型、管腔B型和三阴性乳腺癌内在亚型中的预后良好与预后不良亚组分开。在乳腺癌中，CURIO除了常规使用的诊断方法和因素外，还提供了额外的预后信息。（Cancer Sci 2011; 102：22482254）
The elevated expression of claudins (CLDN) and E-cadherin (CDH-1) was found to correlate with poor prognostic features. Our aim was to perform a comprehensive analysis to assess their potential to predict prognosis in breast cancer. The expression of CLDN-1, -35, -7, -8, -10, -15, -18, and E-cadherin at the mRNA level was evaluated in correlation with survival in datasets containing expression measurements of 1809 breast cancer patients. The breast cancer tissues of 197 patients were evaluated with tissue microarray technique and immunohistochemical method for CLDN-15, -7, and E-cadherin protein expression. An additional validation set of 387 patients was used to test the accuracy of the resulting prognostic score. Based on the bioinformatic screening of publicly-available datasets, the metagene of CLDN-3, -4, -7, and E-cadherin was shown to have the most powerful predictive power in the survival analyses. An immunohistochemical protein profile consisting of CLDN-2, -4, and E-cadherin was able to predict outcome in the most effective manner in the training set. Combining the overlapping members of the above two methods resulted in the claudin-4 and E-cadherin score (CURIO), which was able to accurately predict relapse-free survival in the validation cohort (P = 0.029). The multivariate analysis, including clinicopathological variables and the CURIO, showed that the latter kept its predictive power (P = 0.040). Furthermore, the CURIO was able to further refine prognosis, separating good versus poor prognosis subgroups in luminal A, luminal B, and triple-negative breast cancer intrinsic subtypes. In breast cancer, the CURIO provides additional prognostic information besides the routinely utilized diagnostic approaches and factors. (Cancer Sci 2011; 102: 22482254)