基于不同数据库来源数据的胃癌长链非编码RNA预后预测模型构建
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党胜春, Email: dscgu@163.com

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江苏省镇江市重点研发计划-社会发展基金资助项目(SH2019061)。


Construction of prognostic prediction model for gastric cancer based on aggregate data from multiple databases
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    摘要:

    背景与目的:长链非编码RNA(lncRNA)对于胃癌患者的预后判断有着非常显著的影响。本研究旨在通过生物信息学的方法,构建并验证能够准确评估胃癌患者预后的lncRNA预后预测模型。
    方法:通过癌症基因组图谱(TCGA)数据库、基因型-组织表达数据库(GTEx)获取数据作为用于构建预后模型(建模组),通过基因表达汇编数据库(GEO)获取数据用于验证(验证组)。采用R软件中的edgeR包筛选差异表达lncRNA;通过单因素和多因素Cox回归来构建预后模型并计算风险值;按照风险值的大小将患者分为高、低风险组,分析风险值与临床病理参数及预后的关系。用验证组样本对建模组的结果进行验证。
    结果:共筛选出288个差异表达lncRNA,其中28个与胃癌预后有关(均P<0.05)。10种lncRNA生物标记物(MEG3、DNAJC9-AS1、ACTA2-AS1、C15orf54、LINC01210、OVAAL、POU6F2-AS2、ERICH3-AS1、LINC00326及LINC01526)被鉴定并用于构建预后模型。高风险组的总体生存率以及无病生存率均低于低风险组(均P<0.01),ROC曲线证实该预测模型有一定的准确性(AUC=0.700)。单因素及多因素Cox回归分析显示风险值为独立的预后因子(均P<0.001)。风险值与胃癌T分期(P=0.031)、肿瘤分化程度(P=0.044)存在明显关系。在独立的验证组中,高风险组的总体生存率以及无病生存率同样明显低于低风险组,且示风险值依旧为独立的预后因子(均P<0.05)。
    结论:所构建的10-lncRNA模型对于胃癌患者的预后生存判断有一定的价值,且筛选出的差异表达lncRNA为胃癌分子机制的深入研究提供了依据。

    Abstract:

    Background and Aims: Long non-coding RNAs (lncRNAs) exert significant influences on the prognosis of gastric cancer patients. This study was designated to construct a lncRNA-based prediction model for accurately evaluating the prognosis of gastric cancer patients through bioinformatics approaches. 
    Methods: The data obtained from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases were used for constructing the prognosis model (modeling group), while the data from The Gene Expression Omnibus (GEO) database were used for validation (validation group). The differentially expressed lncRNAs were screened using edgeR package in R software. Univariate and multivariate Cox regression were used to evaluate the association between LncRNA and survival time. prognostic model was created through univariate and multivariate Cox regression analyses and the risk score were calculated. The patients were divided into high-risk group and low-risk group according to their risk scores, and the relations of the risk score with clinicopathologic variables and prognosis were analyzed. The results of the modeling group were verified in the sample from validation group.
    Results: A total of 288 differentially expressed lncRNAs were screened, and 28 of them were associated with the prognosis of gastric cancer (all P<0.05). Ten lncRNA biomarkers (MEG3, DNAJC9-AS1, ACTA2-AS1, C15orf54, LINC01210, OVAAL, POU6F2-AS2, ERICH3-AS1, LINC00326 and LINC01526) were identified and used to construct a prognostic model. Both overall survival rate and disease-free survival rate in high-risk group were significantly lower than those in low-risk group (both P<0.01). ROC curve confirmed that the prediction model had certain accuracy (AUC=0.700). The results of univariate and multivariate Cox regression analyses showed that the risk score was an independent prognostic factor (both P<0.001). The risk score had significant relation with T stage (P=0.031) and the degree of tumor differentiation (P=0.044). In validation cohort, the overall survival rate and disease-free survival rate in high-risk group were also lower than those in low-risk group, and the risk score remained an independent prognostic factor (all P<0.05). 
    Conclusion: The constructed 10-lncRNA model has certain value in predicting the prognosis of gastric cancer patients, and the screened differentially expressed lncRNAs also provide the basis for further investigating the molecular mechanism of gastric cancer.

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周新童, 党胜春.基于不同数据库来源数据的胃癌长链非编码RNA预后预测模型构建[J].中国普通外科杂志,2020,29(10):1187-1194.
DOI:10.7659/j. issn.1005-6947.2020.10.005

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  • 收稿日期:2020-03-28
  • 最后修改日期:2020-10-16
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  • 在线发布日期: 2020-10-25