用于膀胱癌预后预测的lncRNA分子标记物开发

doi:10.24920/003662

摘要/Abstract

摘要：

目的探讨与膀胱癌预后相关的长链非编码RNA (lncRNA)分子标志物,建立膀胱癌患者的预后预测模型。
方法从TCGA数据库中下载膀胱癌患者lncRNA的表达数据。使用单变量Cox回归和基于似然的生存分析发现预后相关的lncRNA分子标记。通过共表达分析和代谢通路富集分析对预后相关的lncRNA进行功能研究。采用多变量Cox回归分析建立风险评分模型,ROC分析确定模型的最佳分界点。通过Kaplan-Meier估计法和log-rank检验对风险评分模型进行验证。
结果我们发现7个预后相关的lncRNA标记(OCIAD1-AS1, RP11-111J6.2, AC079354.3, RP11-553A21.3, RP11-598F7.3, CYP4F35P, RP11-113K21.4)可以预测膀胱癌患者的生存期。通过对这些lncRNA的特点、其靶基因的共表达和代谢通路分析进一步揭示了lncRNA在膀胱癌的发生和发展中发挥重要作用。此外,我们建立并验证了基于7个lncRNA分子标记的的膀胱癌患者预后预测风险评分模型。值得注意的是,我们首次发现了两种与肿瘤相关的反义lncRNA (OCIAD1-AS1和RP11-553A21.3)在膀胱癌预后中的潜在意义。
结论这些lncRNA分子标记可作为治疗膀胱癌的潜在靶点,值得进一步进行功能验证研究。

关键词: 膀胱癌, 长链非编码RNA, 预后, 生存期, 预测

Abstract:

Objective To explore novel long non-coding RNA (lncRNA) molecular markers related to bladder cancer prognosis and to construct a prognostic prediction model for bladder cancer patients.
Methods LncRNA expression data of patients with bladder cancer were downloaded from TCGA database. Univariate Cox regression and likelihood-based survival analysis were used to discover prognosis related lncRNAs. Functional studies of prognosis related lncRNAs were conducted by co-expression analysis and pathway enrichment analysis. Multivariate Cox regression analysis was used to establish risk score model, and Receiver Operating Characteristic analysis was used to determine the optimal cut-off point of the model. The risk score model was validated through Kaplan Meier estimation method and log-rank test.
Results Seven prognosis related lncRNAs (OCIAD1-AS1, RP11-111J6.2, AC079354.3, RP11-553A21.3, RP11-598F7.3, CYP4F35P and RP11-113K21.4) which can predict survival of bladder cancer patient were discovered. Co-expression analysis and pathway analysis of these novel lncRNA signature and their target genes further revealed that these lncRNAs play important roles in the occurrence and development of bladder cancer. Additionally, a seven-lncRNA signature based risk score model for prognostic prediction of bladder cancer patients was established and validated. Notably, we identified the potential significance of two tumor-related antisense lncRNAs (OCIAD1-AS1 and RP11-553A21.3) in the prognosis of bladder cancer.
Conclusion Our results suggest that these lncRNA markers may serve as potential prognosis predictors for bladder cancer and deserve further functional verification studies.

Key words: bladder cancer, long non-coding RNA, prognosis, survival, prediction

Li Wenxing, Zhang Yanli. Novel Long Non-coding RNA Markers for Prognostic Prediction of Patients with Bladder Cancer[J].Chinese Medical Sciences Journal, 2020, 35(3): 239-247.

图/表 5

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Ensembl ID	Gene symbol	Hazard ratio	P value	- logL	AIC
ENSG00000248256.1	OCIAD1-AS1	0.352498	0.000426	313.55	629.1
ENSG00000260331.1	RP11-111J6.2	0.124571	0.000367	309.8	623.61
ENSG00000222035.3	AC079354.3	132322.9	9.81E-06	304.4	614.79
ENSG00000231652.2	RP11-553A21.3 (AL590428.1)	28.95384	4.98E-05	300.78	609.56
ENSG00000256948.1	RP11-598F7.3	0.324872	0.012715	293.77	597.55
ENSG00000265787.1	CYP4F35P	0.473391	0.001861	291.21	594.41
ENSG00000255503.1	RP11-113K21.4	0.15136	0.000223	289.07	592.15

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