Gene expression profiles predict survival and progression of pleural mesothelioma
Gene expression profiles predict survival and progression of pleural mesothelioma
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DOI：
10.1158/1078-0432.ccr-0607-3
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发表时间：
2004-02-01
影响因子：
11.5
通讯作者：
Draghici, S
中科院分区：
文献类型：
--
作者：
Pass, HI;Liu, ZD;Draghici, S
目的：恶性胸膜间皮瘤（MPM）手术患者的临床结果是不准确的预测组织病理学和术中分期。我们假设，基因表达谱可以预测时间的进展和生存在手术cytoreduced胸膜间皮瘤的所有stages.Experimental设计：基因表达分析从21例MPM患者有cytoreductions和相同的术后辅助治疗进行了使用U95 Affytoreduced基因芯片。使用dChip和SAM，神经网络构建了一个常见的27个基因分类器，该分类器与高风险和低风险患者组相关。使用实时PCR和免疫组织化学染色验证数据。27个基因分类器也被用于验证在一个单独的一组17 MPM患者从另一个institution.Results：由基因分类器预测的组概括的实际时间进展和生存的测试集，95.2%的准确性，使用10倍交叉验证。临床结果与组织学无关，早期患者的进展和生存异质性由分类器定义。基因分类器有76%的准确性在单独的验证集MPMs.Conclusions：这些数据表明，间皮瘤活检的治疗前基因表达分析可以预测哪些患者可能受益于手术方法。
Purpose: Clinical outcomes for malignant pleural mesothelioma (MPM) patients having surgery are imprecisely predicted by histopathology and intraoperative staging. We hypothesized that gene expression profiles could predict time to progression and survival in surgically cytoreduced pleural mesothelioma of all stages.Experimental Design: Gene expression analyses from 21 MPM patients having cytoreductions and identical postoperative adjuvant therapy were performed using the U95 Affymetrix gene chip. Using both dChip and SAM, neural networks constructed a common 27 gene classifier, which was associated with either the high-risk and low-risk group of patients. Data were validated using real-time PCR and immunohistochemical staining. The 27 gene classifier was also used for validation in a separate set of 17 MPM patients from another institution.Results: The groups predicted by the gene classifier recapitulated the actual time to progression and survival of the test set with 95.2% accuracy using 10-fold cross-validation. Clinical outcomes were independent of histology, and heterogeneity of progression and survival in early stage patients was defined by the classifier. The gene classifier had a 76% accuracy in the separate validation set of MPMs.Conclusions: These data suggest that pretherapy gene expression analysis of mesothelioma biopsies may predict which patients may benefit from a surgical approach.