Zong Zhen, Hu Ce-Gui, Zhou Tai-Cheng, Yu Zhuo-Min, Tang Fu-Xin, Tian Hua-Kai, Li Hui, Wang He
Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi Province, China.
Department of Gastrointestinal Surgery and Hernia Center, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou 510655, Guangdong Province, China.
World J Gastrointest Surg. 2021 Feb 27;13(2):210-221. doi: 10.4240/wjgs.v13.i2.210.
Investigating molecular biomarkers that accurately predict prognosis is of considerable clinical significance. Accumulating evidence suggests that long non-coding ribonucleic acids (lncRNAs) are frequently aberrantly expressed in colorectal cancer (CRC).
To elucidate the prognostic function of multiple lncRNAs serving as biomarkers in CRC.
We performed lncRNA expression profiling using the lncRNA mining approach in large CRC cohorts from The Cancer Genome Atlas (TCGA) database. Receiver operating characteristic analysis was performed to identify the optimal cutoff point at which patients could be classified into the high-risk or low-risk groups. Based on the Cox coefficient of the individual lncRNAs, we identified a nine-lncRNA signature that was associated with the survival of CRC patients in the training set ( = 175). The prognostic value of this nine-lncRNA signature was validated in the testing set ( = 174) and TCGA set ( = 349). The prognostic models, consisting of these nine CRC-specific lncRNAs, performed well for risk stratification in the testing set and TCGA set. Time-dependent receiver operating characteristic analysis indicated that this predictive model had good performance.
Multivariate Cox regression and stratification analysis demonstrated that this nine-lncRNA signature was independent of other clinical features in predicting overall survival. Functional enrichment analysis of Kyoto Encyclopedia of Genes and Genomes pathways and Gene Ontology terms further indicated that these nine prognostic lncRNAs were closely associated with carcinogenesis-associated pathways and biological functions in CRC.
A nine-lncRNA expression signature was identified and validated that could improve the prognosis prediction of CRC, thereby providing potential prognostic biomarkers and efficient therapeutic targets for patients with CRC.
研究能够准确预测预后的分子生物标志物具有重要的临床意义。越来越多的证据表明，长链非编码核糖核酸（lncRNAs）在结直肠癌（CRC）中经常异常表达。
阐明多种lncRNAs作为生物标志物在CRC中的预后功能。
我们使用lncRNA挖掘方法对来自癌症基因组图谱（TCGA）数据库的大型CRC队列进行lncRNA表达谱分析。进行受试者工作特征分析以确定将患者分为高风险或低风险组的最佳截断点。基于单个lncRNAs的Cox系数，我们在训练集（n = 175）中确定了一个与CRC患者生存相关的九lncRNA特征。该九lncRNA特征的预后价值在测试集（n = 174）和TCGA集（n = 349）中得到验证。由这九个CRC特异性lncRNAs组成的预后模型在测试集和TCGA集中的风险分层表现良好。时间依赖性受试者工作特征分析表明该预测模型具有良好的性能。
多变量Cox回归和分层分析表明，该九lncRNA特征在预测总生存方面独立于其他临床特征。京都基因与基因组百科全书通路和基因本体术语的功能富集分析进一步表明，这九个预后lncRNAs与CRC中与致癌相关的通路和生物学功能密切相关。
确定并验证了一种九lncRNA表达特征，其可改善CRC的预后预测，从而为CRC患者提供潜在的预后生物标志物和有效的治疗靶点。
