Development of a risk model for colon adenocarcinoma based on 3 methylation-regulated long non-coding RNA
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摘要:
目的 本研究通过挖掘癌症基因组图谱(the cancer genome atlas, TCGA)数据库和基因表达公共数据库(gene expression omnibus, GEO)，鉴定结肠腺癌(colon adenocarcinoma, COAD)中甲基化调控的长链非编码RNA(long non-coding RNA, lncRNA)并判断其预后价值。 方法 从TCGA数据库下载COAD患者的表达谱数据、DNA甲基化数据以及相应的临床数据。从GEO数据库下载GSE39582队列表达谱数据。使用R 4.0软件，通过“edgeR”和“limma”包筛选差异表达基因并通过Spearman秩次相关判断基因表达值和甲基化值的相关性。使用Cox回归模型构建风险模型。 结果 通过对TCGA和GEO数据库的联合分析，鉴定出23个甲基化调控的lncRNA。单因素Cox分析鉴定出4个甲基化调控的lncRNA(LINC00675、LINC01082、LINC01207和RP1-170O19.14)与COAD患者的总生存期(overall survival，OS)相关。采用逐步Cox回归分析构建风险模型，风险评分=(-0.148 19×表达量LINC01082)+(-0.120 50×表达量LINC01207)+(-0.120 46×表达量RP1-170O19.14)。 结论 本研究基于甲基化调控的lncRNA构建COAD患者的风险模型，可以促进对COAD患者OS的个体化预测。 Abstract:Objective The purpose of this study is to identify the methylation-regulated long non-coding RNA (lncRNA) in patients with colon adenocarcinoma (COAD) and its prognostic value by mining the cancer genome atlas (TCGA) and gene expression omnibus (GEO). Methods Gene expression profile data, DNA methylation data and corresponding clinical data were obtained from the TCGA. The expression profile data of GSE39582 array was downloaded from the GEO. The edgeR and limma packages were used to screen differentially expressed genes. Spearman rank correlation was used to determine the correlation between gene expression values and methylation values. Cox regression model was used to construct risk model. Results Through joint analysis of TCGA and GEO databases, 23 methylation-regulated lncRNA were identified. Univariate Cox analysis identified 4 methylation-regulated lncRNA (LINC00675, LINC01082, LINC01207, and RP1-170O19.14) associated with overall survival (OS) in COAD patients. A risk model was constructed based on stepwise Cox regression analysis, risk score=(-0.148 19×expression valueLINC01082)+(-0.120 50×expression valueLINC01207)+(-0.120 46×expression valueRP1-170O19.14). Conclusion In this study, the risk model of COAD patients are constructed based on methylation-regulated lncRNA, which could promote the individual prediction of OS in COAD patients. -
Key words:
- Methylation /
- Colon adenocarcinoma /
- Risk model /
- Long non-coding RNA /
- TCGA
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图 1 DElncRNS的识别
注：a：TCGA的DElncRNS；b：GSE39582的DElncRNS；c：TCGA和GSE39582重叠的DElncRNS。
Figure 1. Identification of DElncRNS
图 2 COAD患者风险模型的构建
注：a: COAD患者的风险评分分布、生存状况和风险热图; b: 高低风险组患者的K-M曲线; c: 1年、2年和5年的时间依赖性ROC曲线; d: 在GSE39582中验证风险模型。
Figure 2. Construction of risk model of COAD patients
图 3 COAD患者OS列线图的建立
注：蓝色实线和黑色虚线分别绘制OS的预测概率和实际概率。(a：风险评分和临床变量的Cox回归分析；b：COAD患者的列线图；c：TCGA中列线图的时间依赖性ROC曲线；d：GSE39582中列线图的时间依赖性ROC曲线；e：TCGA中列线图的校准图；f：GSE39582中列线图的校准图)。
Figure 3. Establishment of the OS nomogram for COAD patients
表 1 与COAD患者OS相关的四个甲基化调控的lncRNA
Table 1. Four methylation-regulated long noncoding RNA associated with OS of COAD patients
lncRNA HR(95% CI)值 P值 LINC00675 0.855(0.723~0.998) 0.047 LINC01082 0.824(0.694~0.978) 0.027 LINC01207 0.861(0.751~0.987) 0.031 RP1-170O19.14 0.842(0.721~0.983) 0.030 
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