Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou 510515 Guangdong Province People's Republic of China.
Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou 510515 Guangdong Province People's Republic of China.
Comb Chem High Throughput Screen. 2022;25(5):906-918. doi: 10.2174/1386207324666210302091432.
Hepatocellular carcinoma (HCC) is a malignant tumour with a poor prognosis. The effect of DNA repair on prognosis cannot be ignored, and long non-coding RNA (lncRNA) can regulate the DNA repair process.
To obtain DNA repair-associated lncRNA (DR-lncRNA) prognostic signature for improving the ability to predict HCC prognosis.
Our study used the Cancer Genome Atlas database. Gene set variation analysis was performed to differentiate high and low levels of DNA repair to identify DR-lncRNAs. By performing univariate Cox regression, LASSO regression, and multivariate Cox regression analyses, we finally obtained a DR-lncRNA prognostic signature and constructed a nomogram prognostic model. Time-dependent receiver operating characteristic (ROC) curves, calibration plots, decision curve analysis (DCA), and clinical impact curves were used to assess predictive ability and clinical utility. Differentially expressed genes (DEGs) functional enrichment analysis was performed to further explore the underlying mechanisms that influence HCC prognosis.
We obtained the following DR-lncRNA prognostic signature:AP002478.1, AC116351.1, LINC02580, and LINC00861. The ROC curves and calibration plots showed good discrimination and calibration properties. Combining the DR-lncRNA prognostic signature and tumour stages, we established a nomogram prognostic model. DCA and clinical impact curves showed the clinical utility of this model. DEGs of high-risk and low-risk groups predicted by the prognostic DRlncRNA were significantly associated with cell cycle, various metabolic pathways and biological processes, such as the oxidation-reduction process and cell division.
We identified a DR-lncRNA prognostic signature and constructed a nomogram prognostic model, which could be a beneficial prognostic strategy for HCC.
肝细胞癌(HCC)是一种预后不良的恶性肿瘤。DNA 修复对预后的影响不容忽视,而长链非编码 RNA(lncRNA)可以调节 DNA 修复过程。
获取用于改善 HCC 预后预测能力的与 DNA 修复相关的 lncRNA(DR-lncRNA)预后特征。
本研究使用癌症基因组图谱数据库。采用基因集变异分析对高低水平的 DNA 修复进行区分,以鉴定 DR-lncRNA。通过单变量 Cox 回归、LASSO 回归和多变量 Cox 回归分析,最终获得 DR-lncRNA 预后特征,并构建列线图预后模型。采用时间依赖性接收器工作特征(ROC)曲线、校准图、决策曲线分析(DCA)和临床影响曲线来评估预测能力和临床实用性。对差异表达基因(DEG)的功能富集分析,进一步探讨影响 HCC 预后的潜在机制。
我们获得了以下 DR-lncRNA 预后特征:AP002478.1、AC116351.1、LINC02580 和 LINC00861。ROC 曲线和校准图显示出良好的区分和校准性能。结合 DR-lncRNA 预后特征和肿瘤分期,我们建立了列线图预后模型。DCA 和临床影响曲线显示了该模型的临床实用性。通过预后 DR-lncRNA 预测的高风险和低风险组的 DEG 与细胞周期、各种代谢途径和生物学过程密切相关,如氧化还原过程和细胞分裂。
我们鉴定了一个 DR-lncRNA 预后特征,并构建了一个列线图预后模型,这可能是 HCC 的一种有益的预后策略。