Construction of a genome instability-derived lncRNA-based risk scoring system for the prognosis of hepatocellular carcinoma.
Construction of a genome instability-derived lncRNA-based risk scoring system for the prognosis of hepatocellular carcinoma.
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DOI：
10.18632/aging.203698
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发表时间：
2021-11-18
期刊：
影响因子：
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通讯作者：
Tong GD
中科院分区：
文献类型：
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作者：
Huang DP;Liao MM;Tong JJ;Yuan WQ;Peng DT;Lai JP;Zeng YH;Qiu YJ;Tong GD
新出现的证据揭示了长链非编码RNA（lncRNA）在维持基因组不稳定性中的关键作用。然而，基因组不稳定性相关lncRNA（GILncRNA）及其在肝细胞癌（HCC）的临床预后意义的表现很少报道。本研究构建了一个整合HCC基因组体细胞突变信息和lncRNA表达谱的计算框架，并鉴定了88个HCC的GILncRNA。功能富集分析表明，GILncRNA参与多种代谢过程和肿瘤的基因组不稳定性。使用训练集数据构建基因组不稳定性衍生的基于lncRNA的基因签名（GILncSig）。在测试集和癌症基因组图谱（TCGA）集中验证了GILncSig用于结局预测的性能。多因素考克斯回归分析和分层分析显示GILncSig可作为HCC患者总生存期的独立预后因素。时间依赖性受试者操作特征（ROC）曲线表明GILncSig优于两个最近发表的lncRNA签名的总生存预测。与单独的TP53突变状态相比，GILncSig和肿瘤蛋白p53（TP53）突变状态的组合在生存评估中表现出更好的预后性能。在GILncSig中，AC145343.1被进一步验证为体外HCC的风险因素。总之，本研究为识别基因组不稳定性相关lncRNA提供了一种新的方法，并建立了一个独立的风险评分系统用于HCC患者的预后预测，为深入探讨HCC的发病机制和潜在的治疗策略提供了新的思路。
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 in vitro among GILncSig. 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.