Department of Clinical Laboratory, The Second Hospital of Shandong University, Jinan, Shandong, China.
Tumor Marker Detection Engineering Technology Research Center of Shandong Province, Jinan, Shandong, China.
Aging (Albany NY). 2020 Feb 12;12(3):2857-2879. doi: 10.18632/aging.102782.
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 <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 . Our three-lncRNA signature-based nomogram effectively predicts the prognosis of BCa patients, and could potentially be used for individualized management of such patients.
膀胱癌(BCa)是一种具有多种肿瘤发生机制和临床行为的异质性疾病。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膀胱癌特异性长非编码 RNA(lncRNA)的列线图,以改善 BCa 的生存预测。我们从癌症基因组图谱数据库中获得了 414 名 BCa 患者的大规模基因表达谱。使用 lncRNA 挖掘计算框架,我们在 BCa 与正常样本之间差异表达的 826 个 lncRNA 中鉴定出三个与 OS 相关的 lncRNA。然后,我们构建了一个三-lncRNA 特征,该特征能够有效地将高风险患者与低风险患者区分开来,甚至在 TNM 分期-II、TNM 分期-III 和≥65 岁亚组中也是可行的(均<0.05)。使用临床危险因素,我们开发了基于特征的列线图,该列线图在预后预测方面优于分子特征或临床因素单独使用。生物信息学分析表明,三个与 OS 相关的 lncRNA 与参与细胞外基质组织的基因共表达。功能测定表明,三个与 OS 相关的 lncRNA 之一的 RNF144A-AS1 促进了 BCa 细胞的迁移和侵袭。我们的基于三-lncRNA 特征的列线图可以有效地预测 BCa 患者的预后,并且可能用于此类患者的个体化管理。