Validated prediction of clinical outcome in sarcomas and multiple types of cancer on the basis of a gene expression signature related to genome complexity
Validated prediction of clinical outcome in sarcomas and multiple types of cancer on the basis of a gene expression signature related to genome complexity
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DOI：
10.1038/nm.2174
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发表时间：
2010-07-01
期刊：
影响因子：
82.9
通讯作者：
Aurias, Alain
中科院分区：
文献类型：
--
作者：
Chibon, Frederic;Lagarde, Pauline;Aurias, Alain
肉瘤是一种异质性的侵袭性间质肿瘤。到目前为止，组织学分级是无转移生存的最佳预测指标，但它有一些局限性，如可重复性适中，对某些组织学类型的预后价值较差。为了提高患者的分级，我们对183例肉瘤进行了基因组和表达谱分析，并建立了预后基因表达特征，即肉瘤复杂性指数（CINSARC），由67个与有丝分裂和染色体管理相关的基因组成。在一项多变量分析中，CINSARC预测了训练集和127个独立肉瘤验证集的转移结果。在确定肉瘤患者的转移预后方面，该方法优于法国癌症控制中心联合会（Federation Francaise des Centres de Lutte contrle Cancer）分级系统。此外，它还可以预测胃肠道间质瘤（gist）、乳腺癌和淋巴瘤的预后。该签名的应用将允许对肉瘤患者更有选择性地使用辅助治疗，从而降低医源性发病率并改善这些个体的预后。
Sarcomas are heterogeneous and aggressive mesenchymal tumors. Histological grading has so far been the best predictor for metastasis-free survival, but it has several limitations, such as moderate reproducibility and poor prognostic value for some histological types. To improve patient grading, we performed genomic and expression profiling in a training set of 183 sarcomas and established a prognostic gene expression signature, complexity index in sarcomas (CINSARC), composed of 67 genes related to mitosis and chromosome management. In a multivariate analysis, CINSARC predicts metastasis outcome in the training set and in an independent 127 sarcomas validation set. It is superior to the Federation Francaise des Centres de Lutte Contre le Cancer grading system in determining metastatic outcome for sarcoma patients. Furthermore, it also predicts outcome for gastrointestinal stromal tumors (GISTs), breast carcinomas and lymphomas. Application of the signature will permit more selective use of adjuvant therapies for people with sarcomas, leading to decreased iatrogenic morbidity and improved outcomes for such individuals.