Development of a novel six-long noncoding RNA signature predicting survival of patients with bladder urothelial carcinoma
Development of a novel six-long noncoding RNA signature predicting survival of patients with bladder urothelial carcinoma
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开发预测膀胱尿路上皮癌患者生存的新型六长非编码 RNA 特征
DOI：
10.1002/jcb.29285
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发表时间：
2019-07-24
影响因子：
4
通讯作者：
Zhang, Yingai
中科院分区：
文献类型：
--
作者：
Gao, Xin;Zhang, Shufang;Zhang, Yingai
膀胱尿路上皮癌是泌尿系的一种高发恶性肿瘤。大量研究表明，长链非编码RNA（lncRNA）在膀胱尿路上皮癌的发生、发展中起重要作用。本研究从The Cancer Genome Atlas数据库中获得377例膀胱尿路上皮癌患者的lncRNA表达和临床资料，并对癌组和正常组中差异表达的lncRNA进行评价。对训练数据集中差异表达的lncRNA进行预后的单变量考克斯和多变量考克斯回归分析，评估六种肿瘤相关lncRNA（LINC 02195、LINC 01484、LINC 01468、SMC 2-AS 1、AC 011298.1和PTPRD-AS 1），并构建六种lncRNA签名。在测试数据集和整个数据集中验证了该6-lncRNA签名的预测能力。在多变量考克斯回归和与其他临床因素的分层分析后，6-lncRNA标记的预后能力与其他临床因素无关。我们用六种与乳腺癌相关的lncRNA进行了功能富集分析。功能富集结果显示，这些凋亡相关lncRNA可能促进膀胱尿路上皮癌的发生和转移。综上所述，我们开发的six-lncRNA标签可以有效地预测膀胱尿路上皮癌患者的预后。这种6-lncRNA标记可能是膀胱尿路上皮癌的一种新的独立预后标志物。此外，它也提供了新的见解膀胱尿路上皮癌的机制。
Bladder urothelial carcinoma is a malignant tumor with a high incidence in the uropoietic system. Considerable studies have shown that long noncoding RNA (lncRNA) plays an important role in the development and progression of bladder urothelial carcinoma. In this study, the lncRNA expression and clinical data of 377 bladder urothelial carcinoma patients were obtained from The Cancer Genome Atlas database and differentially expressed lncRNAs in cancer and normal groups were evaluated. Univariate COX and multivariate COX regression analyses of prognosis were performed on differentially expressed lncRNAs in the training data sets, six prognosis-related lncRNAs (LINC02195, LINC01484, LINC01468, SMC2-AS1, AC011298.1, and PTPRD-AS1) were assessed, and a six-lncRNA signature was constructed. The predictive capability of this six-lncRNA signature was validated in the testing data sets and entire data sets. The prognostic ability of the six-lncRNA signature was independent of other clinical elements after multivariate COX regression and stratified analyses of with other clinical elements. We performed functional enrichment analysis with the six prognosis-related lncRNAs. Results of functional enrichment revealed that these prognosis-related lncRNAs might promote the development and metastasis of bladder urothelial carcinoma. In summary, the six-lncRNA signature that we developed could effectively predict the prognosis of bladder urothelial carcinoma patients. This six-lncRNA signature might be a novel independent prognostic marker of bladder urothelial carcinoma. Moreover, it also provides novel insights into the mechanism of bladder urothelial carcinoma.