Liang Yingchun, Ye Fangdie, Cheng Zhang, Ou Yuxi, Zou Lujia, Hu Yun, Hu Jimeng, Jiang Haowen
Departments of Urology, Huashan Hospital, Fudan University, No. 12 WuLuMuQi Middle Road, Shanghai, 200040, China.
Fudan Institute of Urology, Huashan Hospital, Fudan University, Shanghai, China.
Cancer Cell Int. 2021 Sep 8;21(1):476. doi: 10.1186/s12935-021-02185-3.
Muscle-invasive bladder cancer (MIBC) is one of the most important type of bladder cancer, with a high morbidity and mortality rate. Studies have found that long non-coding RNA (lncRNA) plays a key role in maintaining genomic instability. However, Identification of lncRNAs related to genomic instability (GIlncRNAs) and their clinical significance in cancers have not been extensively studied yet.
Here, we downloaded the lncRNA expression profiles, somatic mutation profiles and clinical related data in MIBC patients from The Cancer Genome Atlas (TCGA) database. A lncRNA computational framework was used to find differentially expressed GIlncRNAs. Multivariate Cox regression analysis was used to construct a genomic instability-related lncRNA signature (GIlncSig). Univariate and multivariate Cox analyses were used to assess the independent prognostic for the GIlncSig and other key clinical factors.
We found 43 differentially expressed GIlncRNAs and constructed the GIlncSig with 6 GIlncRNAs in the training cohort. The patients were divided into two risk groups. The overall survival of patients in the high-risk group was lower than that in the low-risk group (P < 0.001), which were further verified in the testing cohort and the entire TCGA cohort. Univariate and multivariate Cox regression showed that the GIlncSig was an independent prognostic factor. In addition, the GIlncSig correlated with the genomic mutation rate of MIBC, indicating its potential as a measure of the degree of genomic instability. The GIlncSig was able to divide FGFR3 wild- and mutant-type patients into two risk groups, and effectively enhanced the prediction effect.
Our study introduced an important reference for further research on the role of GIlncRNAs, and provided prognostic indicators and potential biological therapy targets for MIBC.
肌层浸润性膀胱癌（MIBC）是膀胱癌最重要的类型之一，发病率和死亡率都很高。研究发现，长链非编码RNA（lncRNA）在维持基因组不稳定中起关键作用。然而，与基因组不稳定相关的lncRNA（GIlncRNAs）及其在癌症中的临床意义尚未得到广泛研究。
在此，我们从癌症基因组图谱（TCGA）数据库下载了MIBC患者的lncRNA表达谱、体细胞突变谱和临床相关数据。使用lncRNA计算框架来寻找差异表达的GIlncRNAs。采用多变量Cox回归分析构建基因组不稳定相关的lncRNA特征（GIlncSig）。使用单变量和多变量Cox分析来评估GIlncSig和其他关键临床因素的独立预后。
我们在训练队列中发现了43个差异表达的GIlncRNAs，并构建了包含6个GIlncRNAs的GIlncSig。患者被分为两个风险组。高风险组患者的总生存期低于低风险组（P < 0.001），这在测试队列和整个TCGA队列中得到了进一步验证。单变量和多变量Cox回归显示，GIlncSig是一个独立的预后因素。此外，GIlncSig与MIBC的基因组突变率相关，表明其作为基因组不稳定程度衡量指标的潜力。GIlncSig能够将FGFR3野生型和突变型患者分为两个风险组，并有效增强预测效果。
我们的研究为进一步研究GIlncRNAs的作用提供了重要参考，并为MIBC提供了预后指标和潜在的生物治疗靶点。
