Department of Hepatology, Shenzhen Traditional Chinese Medicine Hospital, The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen 518033, Guangdong Province, China.
College of Basic Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510403, Guangdong, China.
Aging (Albany NY). 2021 Nov 18;13(22):24621-24639. doi: 10.18632/aging.203698.
Emerging evidence revealed the critical roles of long non-coding RNAs (lncRNAs) in maintaining genomic instability. However, genome instability-associated lncRNAs (GILncRNAs) and their performance in clinical prognostic significance in hepatocellular carcinoma (HCC) are rarely reported. Our study constructed a computational framework integrating somatic mutation information and lncRNA expression profiles of HCC genome and we identified 88 GILncRNAs of HCC. Function enrichment analysis revealed that GILncRNAs were involved in various metabolism processes and genome instability of cancer. A genome instability-derived lncRNA-based gene signature (GILncSig) was constructed using training set data. The performance of GILncSig for outcome prediction was validated in testing set and The Cancer Genome Atlas (TCGA) set. The multivariate cox regression analysis and stratification analysis demonstrated GILncSig could serve as an independent prognostic factor for the overall survival of HCC patients. The time-dependent Receiver Operating Characteristic (ROC) curve illustrated GILncSig outperformed two recently published lncRNA signatures for overall survival prediction. The combination of GILncSig and tumor protein p53 (TP53) mutation status exhibited better prognostic performance in survival evaluation compared to TP53 mutation status alone. AC145343.1 was further validated to be a risk factor for HCC . Overall, our study provided a novel approach for identification of genome instability-associated lncRNAs and established an independent risk score system for outcome prediction of HCC patients, which provided a new insight for exploring in-depth mechanism and potential therapy strategy.
越来越多的证据表明长非编码 RNA（lncRNAs）在维持基因组不稳定性方面起着关键作用。然而，与基因组不稳定性相关的 lncRNAs（GILncRNAs）及其在肝细胞癌（HCC）中的临床预后意义尚鲜有报道。我们构建了一个整合 HCC 基因组体细胞突变信息和 lncRNA 表达谱的计算框架，鉴定了 88 个 HCC 的 GILncRNAs。功能富集分析表明，GILncRNAs 参与了各种代谢过程和癌症的基因组不稳定性。使用训练集数据构建了基于基因组不稳定性的 lncRNA 基因特征（GILncSig）。在测试集和癌症基因组图谱（TCGA）集中验证了 GILncSig 对预后的预测性能。多变量 cox 回归分析和分层分析表明，GILncSig 可以作为 HCC 患者总生存期的独立预后因素。时间依赖性接收器操作特征（ROC）曲线表明，GILncSig 在总生存期预测方面优于最近发表的两个 lncRNA 特征。与单独的 TP53 突变状态相比，GILncSig 与 TP53 突变状态的组合在生存评估中表现出更好的预后性能。AC145343.1 进一步被验证为 HCC 的风险因素。总的来说，我们的研究为鉴定与基因组不稳定性相关的 lncRNAs 提供了一种新方法，并建立了一个独立的 HCC 患者预后预测风险评分系统，为深入探索潜在的治疗策略提供了新的思路。
