Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, Changsha, Hunan, China (mainland).
Center for Bioinformatics and Genomics, Department of Biostatistics and Data Science, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA, USA.
Med Sci Monit. 2020 Jun 1;26:e923295. doi: 10.12659/MSM.923295.
BACKGROUND The established clinical criteria for gastric cancer prognosis are insufficient due to molecular heterogeneity. Therefore, constructing a robust prognostic model is essential to predict gastric cancer patient survival. MATERIAL AND METHODS A comprehensive method, which combined weighted gene co-expression network analysis (WGCNA) with elastic-net Cox regression, was utilized to identify prognostic long non-coding RNAs (lncRNAs) from Gene Expression Omnibus database for overall survival (OS) prediction. Methods using WGCNA or elastic-net Cox regression alone were treated as "contrast" methods. The univariate and multivariate Cox regression was used to identify independent prognostic clinical factors. We performed 3-year and 5-year area under the curve (AUC) of the time-dependent receiver operating characteristic comparison of 3 different methods in gene and clinical-gene models to explore the prediction ability of the comprehensive method. The optimal model identified in the training set were validated in the validation set. Biological information analysis for the optimal model was also explored. RESULTS The clinical-gene model containing 13 co-expression lncRNAs identified by the comprehensive method and 3 clinical factors including molecular subtype, recurrence status and operation type, was the found to be the optimal model in the study, with 0.832 and 0.830 for the 3-year and 5-year AUC in the training set, and 0.764 and 0.778 in the validation set, respectively. Biological information analysis suggested that lipid metabolism played an important role in the occurrence and development of gastric cancer. CONCLUSIONS We constructed a novel prognostic model containing 13 co-expression lncRNAs and 3 clinical factors for gastric cancer patients.
由于分子异质性,现有的胃癌预后临床标准还不够完善。因此,构建一个稳健的预后模型对于预测胃癌患者的生存至关重要。
本研究采用综合方法,将加权基因共表达网络分析(WGCNA)与弹性网络 Cox 回归相结合,从基因表达综合数据库中识别出用于总生存期(OS)预测的预后长链非编码 RNA(lncRNA)。单独使用 WGCNA 或弹性网络 Cox 回归的方法被视为“对照”方法。使用单因素和多因素 Cox 回归来确定独立的预后临床因素。我们在基因和临床基因模型中使用 3 种不同方法进行了 3 年和 5 年时间依赖性接受者操作特征曲线(AUC)的比较,以探讨综合方法的预测能力。在验证集中验证了在训练集中确定的最佳模型。还探索了最佳模型的生物学信息分析。
综合方法确定的包含 13 个共表达 lncRNA 和 3 个临床因素(分子亚型、复发状态和手术类型)的临床基因模型是研究中发现的最佳模型,在训练集中的 3 年和 5 年 AUC 分别为 0.832 和 0.830,在验证集中分别为 0.764 和 0.778。生物学信息分析表明,脂质代谢在胃癌的发生和发展中起着重要作用。
本研究构建了一个包含 13 个共表达 lncRNA 和 3 个临床因素的新型胃癌患者预后模型。