Department of Pathology, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, 510095 Guangdong Province, China.
Department of Gastroenterology and Hepatology, Guangzhou Digestive Diseases Center, Guangzhou First People's Hospital, South China University of Technology, Guangzhou, 510180 Guangdong Province, China.
Dis Markers. 2020 Dec 1;2020:9180732. doi: 10.1155/2020/9180732. eCollection 2020.
Our study aims to develop a lncRNA-based classifier and a nomogram incorporating the genomic signature and clinicopathologic factors to help to improve the accuracy of recurrence prediction for hepatocellular carcinoma (HCC) patients.
The lncRNA profiling data of 374 HCC patients and 50 normal healthy controls were downloaded from The Cancer Genome Atlas (TCGA). Using univariable Cox regression and least absolute shrinkage and selection operator (LASSO) analysis, we developed a 15-lncRNA-based classifier and compared our classifier to the existing six-lncRNA signature. Besides, a nomogram incorporating the genomic classifier and clinicopathologic factors was also developed. The predictive accuracy and discriminative ability of the genomic-clinicopathologic nomogram were determined by a concordance index (C-index) and calibration curve and were compared with the TNM staging system by the C-index and receiver operating characteristic (ROC) analysis. Decision curve analysis (DCA) was performed to estimate the clinical value of our nomogram.
Fifteen relapse-free survival (RFS-) related lncRNAs were identified, and the classifier, consisting of the identified 15 lncRNAs, could effectively classify patients into the high-risk and low-risk subgroups. The prediction accuracy of the 15-lncRNA-based classifier for predicting 2-year and 5-year RFS was 0.791 and 0.834 in the training set and 0.684 and 0.747 in the validation set, respectively, which was better than the existing six-lncRNA signature. Moreover, the AUC of genomic-clinicopathologic nomogram in predicting RFS were 0.837 in the training set and 0.753 in the validation set, and the C-index of the genomic-clinicopathologic nomogram was 0.78 (0.72-0.83) in the training set and 0.71 (0.65-0.76) in the validation set, which was better than the traditional TNM stage and 15-lncRNA-based classifier. The decision curve analysis further demonstrated that our nomogram had a larger net benefit than the TNM stage and 15-lncRNA-based classifier. The results were confirmed externally.
Compared to the TNM stage, the 15-lncRNAs-based classifier-clinicopathologic nomogram is a more effective and valuable tool to identify HCC recurrence and may aid in clinical decision-making.
本研究旨在开发一种基于长链非编码 RNA(lncRNA)的分类器和列线图,纳入基因组特征和临床病理因素,以帮助提高肝细胞癌(HCC)患者复发预测的准确性。
从癌症基因组图谱(TCGA)下载了 374 例 HCC 患者和 50 例正常健康对照的 lncRNA 谱数据。使用单变量 Cox 回归和最小绝对值收缩和选择算子(LASSO)分析,我们开发了一个基于 15 个 lncRNA 的分类器,并将我们的分类器与现有的六个 lncRNA 特征进行了比较。此外,还开发了一个包含基因组分类器和临床病理因素的列线图。通过一致性指数(C 指数)和校准曲线来确定基因组-临床病理列线图的预测准确性和判别能力,并通过 C 指数和接受者操作特征(ROC)分析与 TNM 分期系统进行比较。通过决策曲线分析(DCA)来评估我们列线图的临床价值。
确定了 15 个与无复发生存(RFS)相关的 lncRNA,由鉴定出的 15 个 lncRNA 组成的分类器可有效将患者分为高危和低危亚组。基于 15 个 lncRNA 的分类器预测 2 年和 5 年 RFS 的准确性在训练集中分别为 0.791 和 0.834,在验证集中分别为 0.684 和 0.747,优于现有的六个 lncRNA 特征。此外,在训练集中,基因组-临床病理列线图预测 RFS 的 AUC 为 0.837,在验证集中为 0.753,在训练集中,基因组-临床病理列线图的 C 指数为 0.78(0.72-0.83),在验证集中为 0.71(0.65-0.76),优于传统的 TNM 分期和基于 15 个 lncRNA 的分类器。决策曲线分析进一步表明,我们的列线图比 TNM 分期和基于 15 个 lncRNA 的分类器具有更大的净收益。这些结果在外部得到了验证。
与 TNM 分期相比,基于 15 个 lncRNA 的分类器-临床病理列线图是一种更有效、更有价值的识别 HCC 复发的工具,并可能有助于临床决策。