Sequential binary gene ratio tests define a novel molecular diagnostic strategy for malignant pleural mesothelioma.
Sequential binary gene ratio tests define a novel molecular diagnostic strategy for malignant pleural mesothelioma.
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DOI：
10.1158/1078-0432.ccr-12-2117
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发表时间：
2013-05-01
期刊：
影响因子：
--
通讯作者：
Bueno R
中科院分区：
文献类型：
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作者：
De Rienzo A;Richards WG;Yeap BY;Coleman MH;Sugarbaker PE;Chirieac LR;Wang YE;Quackenbush J;Jensen RV;Bueno R
为了开发分子诊断的标准化方法，我们使用基因表达比生物信息技术来设计分子特征，以从其他可能混淆的诊断中诊断 MPM，并将上皮样细胞与 MPM 的肉瘤样组织学亚型区分开来。此外，我们还搜索了 MPM 与其他相关癌症相比的相关通路，以确定 MPM 中独特的分子特征。我们对 113 个标本进行了微阵列分析，包括 MPM 以及一系列肿瘤和良性组织，包括 MPM 的鉴别诊断。我们生成了二元基因表达比率测试的顺序组合，能够将 MPM 与其他胸部恶性肿瘤区分开来。我们将该方法与其他生物信息学工具进行了比较，并在一组独立的 170 个样本中验证了该特征。进行功能富集分析以鉴定差异表达的探针。基因表达比率测试的顺序组合是将 MPM 与所有其他样本区分开来的最佳分子方法。生物信息学和分子验证表明，序贯基因比率测试能够以高灵敏度和特异性识别 MPM 样本。此外，基因比率技术能够区分上皮样和肉瘤样类型的 MPM。鉴定出在 MPM 中特异性激活的新基因和途径。使用少量基因进行了新的临床相关分子测试，以准确地区分 MPM 与其他胸部样本，支持我们的假设，即基因表达比方法可能是癌症鉴别诊断的有用工具。
To develop a standardized approach for molecular diagnostics, we used the gene-expression ratio bioinformatic technique to design a molecular signature to diagnose MPM from among other potentially confounding diagnoses and differentiate the epithelioid from the sarcomatoid histological subtype of MPM. In addition, we searched for pathways relevant in MPM in comparison to other related cancers to identify unique molecular features in MPM. We performed microarray analysis on 113 specimens including MPMs and a spectrum of tumors and benign tissues comprising the differential diagnosis of MPM. We generated a sequential combination of binary gene-expression ratio tests able to discriminate MPM from other thoracic malignancies. We compared this method to other bioinformatic tools and validated this signature in an independent set of 170 samples. Functional enrichment analysis was performed to identify differentially expressed probes. A sequential combination of gene-expression ratio tests was the best molecular approach to distinguish MPM from all the other samples. Bioinformatic and molecular validations showed that the sequential gene ratio tests were able to identify the MPM samples with high sensitivity and specificity. In addition, the gene-ratio technique was able to differentiate the epithelioid from the sarcomatoid type of MPM. Novel genes and pathways specifically activated in MPM were identified. New clinically relevant molecular tests have been generated using a small number of genes to accurately distinguish MPMs from other thoracic samples supporting our hypothesis that the gene-expression ratio approach could be a useful tool in the differential diagnosis of cancers.