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基于RNA测序的8长非编码RNA特征预测食管癌生存情况的鉴定

Identification of a RNA-Seq Based 8-Long Non-Coding RNA Signature Predicting Survival in Esophageal Cancer.

作者信息

Fan Qiaowei, Liu Bingrong

机构信息

Department of Gastroenterology and Hepatology, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China (mainland).

出版信息

Med Sci Monit. 2016 Dec 28;22:5163-5172. doi: 10.12659/msm.902615.

Abstract

BACKGROUND Accumulating evidence suggests the involvement of long non-coding RNAs (lncRNAs) as oncogenic or tumor suppressive regulators in the development of various cancers. In the present study, we aimed to identify a lncRNA signature based on RNA sequencing (RNA-seq) data to predict survival in esophageal cancer. MATERIAL AND METHODS The RNA-seq lncRNA expression data and clinical information were downloaded from The Cancer Genome Atlas (TCGA) database. Differentially expressed lncRNAs were screened out between esophageal cancer and normal tissues. Univariate and multivariate Cox regression analysis were performed to establish a lncRNA-related prognostic model. Receiver operating characteristic (ROC) analysis was conducted to test the sensitivity and specificity of the model. GO (gene ontology) functional and KEGG pathway enrichment analyses were performed for mRNAs co-expressed with the lncRNAs to explore the potential functions of the prognostic lncRNAs. RESULTS A total of 265 differentially expressed lncRNAs were identified between esophageal cancer and normal tissues. After univariate and multivariate Cox regression analysis, eight lncRNAs (GS1-600G8.5, LINC00365, CTD-2357A8.3, RP11-705O24.1, LINC01554, RP1-90J4.1, RP11-327J17.1, and LINC00176) were finally screened out to establish a predictive model by which patients could be classified into high-risk and low-risk groups with significantly different overall survival. Further analysis indicated independent prognostic capability of the 8-lncRNA signature from other clinicopathological factors. ROC curve analysis demonstrated good performance of the 8-lncRNA signature. Functional enrichment analysis showed that the prognostic lncRNAs were mainly associated with esophageal cancer related biological processes such as regulation of glucose metabolic process and amino acid and lipids metabolism. CONCLUSIONS Our study developed a novel candidate model providing additional and more powerful prognostic information beyond conventional clinicopathological factors for survival prediction of esophageal cancer patients. Moreover, it also brings us new insights into the molecular mechanisms underlying esophageal cancer.

摘要

背景 越来越多的证据表明,长链非编码RNA(lncRNA)作为致癌或抑癌调节因子参与了多种癌症的发生发展。在本研究中,我们旨在基于RNA测序(RNA-seq)数据鉴定一种lncRNA特征,以预测食管癌患者的生存情况。

材料与方法 从癌症基因组图谱(TCGA)数据库下载RNA-seq lncRNA表达数据和临床信息。筛选出食管癌组织与正常组织之间差异表达的lncRNA。进行单因素和多因素Cox回归分析,以建立lncRNA相关的预后模型。进行受试者工作特征(ROC)分析,以检验该模型的敏感性和特异性。对与lncRNA共表达的mRNA进行基因本体(GO)功能和京都基因与基因组百科全书(KEGG)通路富集分析,以探索预后lncRNA的潜在功能。

结果 在食管癌组织与正常组织之间共鉴定出265个差异表达的lncRNA。经过单因素和多因素Cox回归分析,最终筛选出8个lncRNA(GS1-600G8.5、LINC00365、CTD-2357A8.3、RP11-705O24.1、LINC01554、RP1-90J4.1、RP11-327J17.1和LINC00176),建立了一个预测模型,可将患者分为高风险组和低风险组,两组患者的总生存期有显著差异。进一步分析表明,这8个lncRNA特征与其他临床病理因素相比具有独立的预后能力。ROC曲线分析显示该8个lncRNA特征具有良好的性能。功能富集分析表明,预后lncRNA主要与食管癌相关的生物学过程有关,如葡萄糖代谢过程的调节以及氨基酸和脂质代谢。

结论 我们的研究开发了一种新的候选模型,为食管癌患者的生存预测提供了超越传统临床病理因素的额外且更强大的预后信息。此外,它还为我们深入了解食管癌的分子机制带来了新的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/811b/5216666/84541ac3b291/medscimonit-22-5163-g001.jpg

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