Low ANXA10 expression is associated with disease aggressiveness in bladder cancer.

Low ANXA10 expression is associated with disease aggressiveness in bladder cancer.
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DOI:
10.1038/bjc.2011.404
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发表时间:
2011-10-25
影响因子:
8.8
通讯作者:
Dyrskjot, L.
Dyrskjot, L.
中科院分区:
医学1区
文献类型:
--
作者:
Munksgaard, P. P.;Mansilla, F.;Eskildsen, A-S Brems;Fristrup, N.;Birkenkamp-Demtroder, K.;Ulhoi, B. P.;Borre, M.;Agerbaek, M.;Hermann, G. G.;Orntoft, T. F.;Dyrskjot, L.

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膀胱癌预后预测的标志物是迫切需要的。我们以前已经确定了一个预测非肌肉浸润性膀胱癌进展的分子标记。ANXA 10是签名中包含的标志物之一,我们现在验证了ANXA 10在蛋白质水平上的预后相关性。我们使用249例Ta和T1尿路上皮癌的组织微阵列通过免疫组织化学研究了ANXA 10的表达。还在另外一组97个更晚期的肿瘤中研究了ANXA 10的表达。使用伤口愈合测定、增殖测定和独创性途径分析,通过siRNA介导的ANXA 10敲低研究ANXA 10在细胞系中的功能作用。ANXA 10的低表达与Ta和T1期肿瘤患者的无进展生存期较短相关(P<0.00001)。此外,晚期肿瘤和ANXA 10低表达的患者预后不良(P<0.00001)。我们发现ANXA10 siRNA转染的细胞与对照siRNA转染的细胞相比生长显著更快。此外,伤口愈合测定显示ANXA 10 siRNA转染的细胞比对照转染的细胞更快地沿伤口边缘沿着。我们的结论是,ANXA 10可能是一个临床相关的标志物,用于预测膀胱癌的早期和晚期阶段的结果。
Markers for outcome prediction in bladder cancer are urgently needed. We have previously identified a molecular signature for predicting progression in non-muscle-invasive bladder cancer. ANXA10 was one of the markers included in the signature and we now validated the prognostic relevance of ANXA10 at the protein level. We investigated ANXA10 expression by immunohistochemistry using a tissue microarray with 249 Ta and T1 urothelial carcinomas. The expression of ANXA10 was also investigated in an additional set of 97 more advanced tumours. The functional role of ANXA10 in cell lines was investigated by siRNA-mediated ANXA10 knockdown using wound-healing assays, proliferation assays, and ingenuity pathway analysis. Low expression of ANXA10 correlated with shorter progression-free survival in patients with stage Ta and T1 tumours (P<0.00001). Furthermore, patients with more advanced tumours and low ANXA10 expression had an unfavourable prognosis (P<0.00001). We found that ANXA10 siRNA transfected cells grew significantly faster compared with control siRNA transfected cells. Furthermore, a wound-healing assay showed that ANXA10 siRNA transfected cells spread along wound edges faster than control transfected cells. We conclude that ANXA10 may be a clinical relevant marker for predicting outcome in both early and advanced stages of bladder cancer.
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