Li Jian, Wei Shimei, Zhang Yan, Lu Shuangshuang, Zhang Xiaoxu, Wang Qiong, Yan Jiawei, Yang Sanju, Chen Liying, Liu Yunguang, Huang Zhijing
Department of Pediatrics, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, China.
Department of Pediatrics, Shanxi Children's Hospital, Taiyuan, China.
Front Genet. 2022 Apr 25;13:874673. doi: 10.3389/fgene.2022.874673. eCollection 2022.
The role of long-chain noncoding RNA (lncRNA) in genomic instability has been demonstrated to be increasingly importance. Therefore, in this study, lncRNAs associated with genomic instability were identified and kidney renal papillary cell carcinoma (KIRP)-associated predictive features were analysed to classify high-risk patients and improve individualised treatment. The training ( = 142) and test ( = 144) sets were created using raw RNA-seq and patient's clinical data of KIRP obtained from The Cancer Genome Atlas (TCGA).There are 27 long-chain noncoding RNAs (lncRNAs) that are connected with genomic instability, these lncRNAs were identified using the 'limma' R package based on the numbers of somatic mutations and lncRNA expression profiles acquired from KIRP TCGA cohort. Furthermore, Cox regression analysis was carried out to develop a genome instability-derived lncRNA-based gene signature (GILncSig), whose prognostic value was confirmed in the test cohort as well as across the entire KIRP TCGA dataset. A GILncSig derived from three lncRNAs (BOLA3-AS1, AC004870, and LINC00839), which were related with poor KIRP survival, was identified, which was split up into high- and low-risk groups. Additionally, the GILncSig was found to be an independent prognostic predictive index in KIRP using univariate and multivariate Cox analysis. Furthermore, the prognostic significance and characteristics of GilncSig were confirmed in the training test and TCGA sets. GilncSig also showed better predictive performance than other prognostic lncRNA features. The function of lncRNAs in genomic instability and the genetic diversity of KIRP were elucidated in this work. Moreover, three lncRNAs were screened for prediction of the outcome of KIRP survival and novel insights into identifying cancer biomarkers related to genomic instability were discussed.
长链非编码RNA（lncRNA）在基因组不稳定性中的作用已被证明越来越重要。因此，在本研究中，鉴定了与基因组不稳定性相关的lncRNA，并分析了肾肾乳头状细胞癌（KIRP）相关的预测特征，以对高危患者进行分类并改善个体化治疗。使用从癌症基因组图谱（TCGA）获得的KIRP原始RNA测序和患者临床数据创建了训练集（n = 142）和测试集（n = 144）。有27个与基因组不稳定性相关的长链非编码RNA（lncRNA），这些lncRNA是使用“limma”R包根据从KIRP TCGA队列获得体细胞突变数量和lncRNA表达谱来鉴定的。此外，进行了Cox回归分析以开发基于基因组不稳定性的lncRNA基因特征（GILncSig），其预后价值在测试队列以及整个KIRP TCGA数据集中得到证实。鉴定出一个由三个与KIRP生存不良相关的lncRNA（BOLA3-AS1、AC004870和LINC00839）衍生的GILncSig，它被分为高风险和低风险组。此外，使用单变量和多变量Cox分析发现GILncSig是KIRP中的一个独立预后预测指标。此外，在训练测试集和TCGA集中证实了GilncSig的预后意义和特征。GilncSig还显示出比其他预后lncRNA特征更好的预测性能。这项工作阐明了lncRNA在基因组不稳定性中的功能以及KIRP的遗传多样性。此外，筛选了三个lncRNA用于预测KIRP生存结果，并讨论了在识别与基因组不稳定性相关的癌症生物标志物方面的新见解。
