Genomic Grade Index predicts postoperative clinical outcome of GIST.
Genomic Grade Index predicts postoperative clinical outcome of GIST.
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DOI：
10.1038/bjc.2012.390
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发表时间：
2012-10-09
影响因子：
8.8
通讯作者：
Birnbaum, D.
中科院分区：
文献类型：
--
作者：
Bertucci, F.;Finetti, P.;Ostrowski, J.;Kim, W. K.;Kim, H.;Pantaleo, M. A.;Astolfi, A.;Polkowski, M.;Birnbaum, D.
局部胃肠道间质瘤（GIST）的预后是不均匀的，特别是对于AFIP复发的中度或高风险患者，他们是辅助伊马替尼的候选人。我们假设基因表达谱可能改善预后，并有助于完善伊马替尼的适应症。我们收集了146例术前单纯手术治疗的局部GIST样本的基因表达和组织临床数据。我们寻找一种预测无复发生存（RFS）的基因表达特征（GES），并将其性能与三种已发表的基于预后增殖的GES（基因组分级指数（GGI）、16-激酶和CINSARC）和AFIP分类进行比较。我们还分析了28例接受新辅助伊马替尼治疗的晚期GIST患者的数据集。我们在学习集中确定了275个基因的基因表达特征（GES）预测RFS，并在独立集中验证了其稳健性。然而，在单因素和多因素分析的两个独立测试集中，GGI的预后表现优于其他两个特征和AFIP中间风险分类。重要的是，GGI可以将AFIP中/高风险样本分为RFS不同的两组。基因组分级指数的“高风险”肿瘤比“低风险”肿瘤更具增殖性和遗传不稳定性，并且对伊马替尼更敏感。GGI改进了局部GIST中RFS的预测，可能有助于定制辅助伊马替尼。
Prognosis of localised gastrointestinal stromal tumour (GIST) is heterogeneous, notably for patients with AFIP intermediate or high risk of relapse, who are candidates to adjuvant imatinib. We hypothesised that gene expression profiles might improve the prognostication and help to refine the indications for imatinib. We collected gene expression and histoclinical data of 146 pre-treatment localised GIST samples treated with surgery alone. We searched for a gene expression signature (GES) predictive for relapse-free survival (RFS) and compared its performances to that of three published prognostic proliferation-based GES (Genomic Grade Index (GGI), 16-Kinase, and CINSARC) and AFIP classification. We also analysed a data set from 28 patients with advanced GIST treated with neo-adjuvant imatinib. We identified a 275-gene GES (gene expression signature) predictive of RFS in a learning set and validated its robustness in an independent set. However, the GGI outperformed its prognostic performances, and those of the two other signatures and the AFIP intermediate-risk classification in two independent tests sets in uni- and multivariate analyses. Importantly, GGI could split the AFIP intermediate/high-risk samples into two groups with different RFS. Genomic Grade Index ‘high-risk’ tumours were more proliferative and genetically unstable than ‘low-risk’ tumours, and more sensitive to imatinib. GGI refines the prediction of RFS in localised GIST and might help tailor adjuvant imatinib.
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影响因子：
6.2
作者：
DeMatteo, Ronald P.;Gold, Jason S.;Antonescu, Cristina R.
通讯作者：
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影响因子：
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影响因子：
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作者：
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通讯作者：
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影响因子：
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作者：
Chibon, Frederic;Lagarde, Pauline;Aurias, Alain
通讯作者：
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