A nomogram combining long non-coding RNA expression profiles and clinical factors predicts survival in patients with bladder cancer
A nomogram combining long non-coding RNA expression profiles and clinical factors predicts survival in patients with bladder cancer
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结合长非编码 RNA 表达谱和临床因素的列线图可预测膀胱癌患者的生存
DOI：
10.18632/aging.102782
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发表时间：
2020-02-15
期刊：
影响因子：
5.2
通讯作者：
Wang, Chuanxin
中科院分区：
文献类型：
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作者：
Wang, Yifan;Du, Lutao;Wang, Chuanxin
膀胱癌（BCa）是一种异质性疾病，具有多种致瘤机制和临床表现。目前的肿瘤淋巴结转移（TNM）分期系统不足以预测BCa患者的总生存期（OS）。我们开发了一种基于BCa特异性长链非编码RNA（lncRNA）的列线图，以改善BCa的生存预测。我们在癌症基因组图谱数据库中获得了414名BCa患者样本的大规模基因表达谱。使用lncRNA-mining计算框架，我们在BCa和正常样本之间差异表达的826个lncRNAs中确定了3个OS相关lncRNAs。然后，我们构建了一个三lncRNA标签，它有效地区分了高风险和低风险患者，甚至在TNM II期，TNM III期和≥65岁的亚组中也是可行的（所有P<0.05）。使用临床风险因素，我们开发了一种基于特征的诺模图，其在预后预测方面优于单独的分子特征或临床因素。生物信息学分析显示，这三个OS相关的lncRNA与细胞外基质组织相关的基因共表达。功能分析表明，RNF 144 A-AS 1，三个OS相关的lncRNA之一，促进BCa细胞的迁移和侵袭在体外。我们的三lncRNA签名为基础的诺模图有效地预测BCa患者的预后，并可能用于此类患者的个体化管理。
Bladder cancer (BCa) is a heterogeneous disease with various tumorigenic mechanisms and clinical behaviors. The current tumor-node-metastasis (TNM) staging system is inadequate to predict overall survival (OS) in BCa patients. We developed a BCa-specific, long-non-coding-RNA (lncRNA)-based nomogram to improve survival prediction in BCa. We obtained the large-scale gene expression profiles of samples from 414 BCa patients in The Cancer Genome Atlas database. Using an lncRNA-mining computational framework, we identified three OS-related lncRNAs among 826 lncRNAs that were differentially expressed between BCa and normal samples. We then constructed a three-lncRNA signature, which efficiently distinguished high-risk from low-risk patients and was even viable in the TNM stage-II, TNM stage-III and ≥65-year-old subgroups (all P<0.05). Using clinical risk factors, we developed a signature-based nomogram, which performed better than the molecular signature or clinical factors alone for prognostic prediction. A bioinformatical analysis revealed that the three OS-related lncRNAs were co-expressed with genes involved in extracellular matrix organization. Functional assays demonstrated that RNF144A-AS1, one of the three OS-related lncRNAs, promoted BCa cell migration and invasion in vitro. Our three-lncRNA signature-based nomogram effectively predicts the prognosis of BCa patients, and could potentially be used for individualized management of such patients.