Development and External Validation of a Novel 12-Gene Signature for Prediction of Overall Survival in Muscle-Invasive Bladder Cancer
Development and External Validation of a Novel 12-Gene Signature for Prediction of Overall Survival in Muscle-Invasive Bladder Cancer
复制标题
用于预测肌层浸润性膀胱癌总体生存率的新型 12 基因特征的开发和外部验证
DOI：
10.3389/fonc.2019.00856
复制
发表时间：
2019-09-06
影响因子：
4.7
通讯作者：
Ye, Dingwei
中科院分区：
文献类型：
--
作者：
Abudurexiti, MierXiati;Xie, Huyang;Ye, Dingwei
目的：我们旨在从已发表的数据中开发和验证一个新的基因标记，并提高对肌肉浸润性膀胱癌（MIBC）生存的预测。方法：我们检索已发表的与MIBC总生存期（OS）相关的基因特征，并对所有274个基因进行编译，形成一个新的基因特征。下载TCGA （Cancer Genome Atlas）膀胱队列的RNAseq数据。所有基因均纳入单因素Cox风险比模型。然后，我们使用了一个简化的多变量Cox回归模型，该模型只包括在单变量模型中P < 0.05的基因。采用复旦大学上海肿瘤中心（FUSCC）的172例患者和GEO数据集的61例患者作为外部验证集。结果：TCGA队列共纳入327例患者。我们从8篇已发表的关于MIBC OS的论文中鉴定出274个基因。利用TCGA数据库，我们确定了12个与OS相关的基因（单因素和多因素分析均P < 0.05）。通过将这些基因与我们验证数据集和GEO数据集中的RT-qPCR数据整合，我们证实了在TCGA和FUSCC队列中，12个基因组预测OS的能力（AUC分别为0.741和0.727）高于单独的临床数据（包括性别、年龄、T分期、分级和N分期）（AUC分别为0.667和0.631）。此外，将临床数据和12个基因面板结合起来，TCGA、FUSCC和GSE13507队列的AUC分别增加到0.768、0.757和0.88。结论：利用已发表的基因签名和TCGA数据，我们成功构建并外部验证了一个新的12个基因的MIBC生存特征。我们系统地回顾了所有已发表的肌肉浸润性膀胱癌（MIBC）的预后基因特征，并整合了TCGA MIBC队列中的基因。这个新的基因面板在新建立的GEO和FUSCC的MIBC队列中得到了验证。这种方法可以帮助以一种新的方式更新以前建立的面板。
Purpose: We aimed to develop and validate a novel gene signature from published data and improve the prediction of survival in muscle-invasive bladder cancer (MIBC). Methods: We searched the published gene signatures associated with the overall survival (OS) of MIBC and compiled all 274 genes to develop a novel gene signature. RNAseq data of TCGA (the Cancer Genome Atlas) bladder cohort were downloaded. All genes were included in a univariate Cox hazard ratio model. We then used a reduced multivariate Cox regression model, which included only genes achieving P < 0.05 in the univariate model. A total of 172 patients at Fudan University Shanghai Cancer Center (FUSCC) and 61 patients from GEO datasets were used as an external validation set. Results: A total of 327 patients in the TCGA cohort were enrolled. We identified 274 genes from eight published papers on the OS of MIBC. Using the TCGA database, we identified 12 genes that correlated with OS (P < 0.05 in both univariate and multivariate analyses). By integrating these genes with the RT-qPCR data in our validation dataset and GEO datasets, we confirmed that the power for predicting OS of the 12-gene panel (AUC of 0.741 and 0.727, respectively) was higher than just clinical data (including gender, age, T stage, grade, and N stage) alone in the TCGA and FUSCC cohort (AUC of 0.667 and 0.631, respectively). Additionally, upon combining the clinical data and 12-gene panel together, the AUC increased to 0.768, 0.757, and 0.88 in the TCGA, FUSCC and GSE13507 cohorts, respectively. Conclusions: Applying published gene signatures and TCGA data, we successfully built and externally validated a novel 12-gene signature for the survival of MIBC. Brief Explanation We systemically reviewed all published prognostic gene signatures of muscle-invasive bladder cancer (MIBC) and integrated the genes in the TCGA MIBC cohort. This new gene panel was validated in a newly established MIBC cohort in GEO and FUSCC. This method can help update the previous established panels in a new way.