Malignant pleural mesothelioma (MPM), predominantly caused by asbestos exposure, is a highly aggressive cancer with poor prognosis. The staging systems currently used in clinics is inadequate in evaluating the prognosis of MPM. In this study, a five-gene signature was developed and enrolled into a prognostic risk score model by LASSO Cox regression analysis based on two expression profiling datasets (GSE2549 and GSE51024) from Gene Expression Omnibus (GEO). The five-gene signature was further validated using the Cancer Genome Atlas (TCGA) MPM dataset. Univariate and multivariate Cox analyses proved that the five-gene signature was an independent prognostic factor for MPM. The signature remained statistically significant upon stratification by Brigham stage, AJCC stage, gender, tumor size, and lymph node status. Time-dependent receiver operating characteristic (ROC) curve indicated good performance of our model in predicting 1- and 2-years overall survival in MPM patients. The C-index was 0.784 for GSE2549 and 0.753 for the TCGA dataset showing moderate predictive accuracy of our model. Furthermore, Gene Set Enrichment Analysis suggested that the five-gene signature was related to pathways resulting in MPM tumor progression. Together, we have established a five-gene signature significantly associated with prognosis in MPM patients. Hence, the five-genes signature may serve as a potentially useful prognostic tool for MPM patients.

恶性胸膜间皮瘤（MPM）主要由石棉暴露引起，是一种高度侵袭性的癌症，预后较差。当前临床中使用的分期系统不足以评估MPM的预后。在这项研究中，基于来自Gene Expression Omnibus（GEO）的两个表达谱数据集（GSE2549和GSE51024），通过LASSO Cox回归分析开发了五基因签名并将其纳入预后风险评分模型。使用癌症基因组图谱（TCGA）MPM数据集进一步验证了五基因签名。单因素和多因素Cox分析证明，五基因签名是MPM的独立预后因素。在通过Brigham分期，AJCC分期，性别，肿瘤大小和淋巴结状态进行分层后，签名仍然具有统计学意义。时间依赖性接收器工作特征（ROC）曲线表明我们的模型在预测MPM患者的1年和2年总生存率方面表现良好。GSE2549的C指数为0.784，TCGA数据集的C指数为0.753，显示了我们模型的中等预测准确性。此外，基因集富集分析表明，五基因签名与导致MPM肿瘤进展的途径有关。我们共同建立了一个五基因标志，与MPM患者的预后显着相关。因此，五基因签名可以作为MPM患者的潜在有用的预后工具。753对于TCGA数据集显示了我们模型的中等预测精度。此外，基因集富集分析表明，五基因签名与导致MPM肿瘤进展的途径有关。我们共同建立了一个五基因标志，与MPM患者的预后显着相关。因此，五基因签名可以作为MPM患者的潜在有用的预后工具。753对于TCGA数据集显示了我们模型的中等预测精度。此外，基因集富集分析表明，五基因签名与导致MPM肿瘤进展的途径有关。我们共同建立了一个五基因标志，与MPM患者的预后显着相关。因此，五基因签名可以作为MPM患者潜在的有用的预后工具。