Analysis of molecular intra-patient variation and delineation of a prognostic 12-gene signature in non-muscle invasive bladder cancer; technology transfer from microarrays to PCR.
Analysis of molecular intra-patient variation and delineation of a prognostic 12-gene signature in non-muscle invasive bladder cancer; technology transfer from microarrays to PCR.
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DOI：
10.1038/bjc.2012.412
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发表时间：
2012-10-09
影响因子：
8.8
通讯作者：
Orntoft, T. F.
中科院分区：
文献类型：
--
作者：
Dyrskjot, L.;Reinert, T.;Novoradovsky, A.;Zuiverloon, T. C. M.;Beukers, W.;Zwarthoff, E.;Malats, N.;Real, F. X.;Segersten, U.;Malmstrom, P-U;Knowles, M.;Hurst, C.;Sorge, J.;Borre, M.;Orntoft, T. F.
已证实多种临床风险因素和遗传谱可预测非肌层浸润性膀胱癌的进展;然而，尚未开发出易于临床应用的基因特征来预测疾病进展，而不依赖于疾病分期和分级。我们使用来自17名患者的39个异时性肿瘤测量了88个基因进展特征的患者内变异。为了描述最佳的定量逆转录酶PCR标记物组，我们使用了来自丹麦、瑞典、英国和西班牙患者的115个肿瘤样本。分子标记物的患者内变异分析显示71%相似的分类结果。最后一组12个基因被选择，显示与结果显著相关。在多变量考克斯回归分析中，我们发现，当调整分期、分级和治疗时，12个基因签名是独立的预后因素（风险比=7.4（95%置信区间：3.4-15.9），P<0.001）。需要对12个基因组和确定的截止值进行独立验证，并且正在进行。异时性肿瘤中存在患者内标记物变异。因此，为了提高检测灵敏度，可能需要检测患者病程中的几种异时性肿瘤。基于PCR的12基因签名可显著预测非肌层浸润性膀胱癌患者的疾病进展
Multiple clinical risk factors and genetic profiles have been demonstrated to predict progression of non-muscle invasive bladder cancer; however, no easily clinical applicable gene signature has been developed to predict disease progression independent of disease stage and grade. We measured the intra-patient variation of an 88-gene progression signature using 39 metachronous tumours from 17 patients. For delineation of the optimal quantitative reverse transcriptase PCR panel of markers, we used 115 tumour samples from patients in Denmark, Sweden, UK and Spain. Analysis of intra-patient variation of the molecular markers showed 71% similar classification results. A final panel of 12 genes was selected, showing significant correlation with outcome. In multivariate Cox regression analysis, we found that the 12-gene signature was an independent prognostic factor (hazard ratio=7.4 (95% confidence interval: 3.4–15.9), P<0.001) when adjusting for stage, grade and treatment. Independent validation of the 12-gene panel and the determined cut-off values is needed and ongoing. Intra-patient marker variation in metachronous tumours is present. Therefore, to increase test sensitivity, it may be necessary to test several metachronous tumours from a patient’s disease course. A PCR-based 12-gene signature significantly predicts disease progression in patients with non-muscle invasive bladder cancer.
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影响因子：
11.2
作者：
Wang R;Morris DS;Tomlins SA;Lonigro RJ;Tsodikov A;Mehra R;Giordano TJ;Kunju LP;Lee CT;Weizer AZ;Chinnaiyan AM
通讯作者：
Chinnaiyan AM
影响因子：
3.1
作者：
Dyrskjot, Lars;Zieger, Karsten;Orntoft, Torben Falck
通讯作者：
Orntoft, Torben Falck
影响因子：
6.6
作者：
Hermann, GG;Horn, T;Steven, K
通讯作者：
Steven, K
影响因子：
158.5
作者：
van de Vijver, MJ;He, YD;Bernards, R
通讯作者：
Bernards, R
影响因子：
7
作者：
Thorsen, Kasper;Sorensen, Karina D.;Orntoft, Torben F.
通讯作者：
Orntoft, Torben F.