The Prognostic Value of m6A RNA Methylation Regulators in Colon Adenocarcinoma

The Prognostic Value of m6A RNA Methylation Regulators in Colon Adenocarcinoma
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DOI:
10.12659/msm.920381
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发表时间:
2019-12-11
影响因子:
3.1
通讯作者:
Wang, Lei
Wang, Lei
中科院分区:
医学4区
文献类型:
--
作者:
Liu, Tao;Li, Chenyao;Wang, Lei

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背景:通过对癌症基因组图谱数据库中331例与临床资料匹配的结直肠腺癌标本的RNA-seq FPKM数据进行分析,以揭示m6A RNA甲基化调节因子在结肠腺癌中的预后价值。通过一致性聚类将样本分为I类和II类。采用主成分分析方法对基因分布进行分析。进一步对选定的m6A RNA基因进行功能分析,并用Lasso-Cox回归算法建立潜在的危险特征。采用最小标准,计算出亚组II的YTHDF1和HNRNPC的危险系数。根据危险特征将患者分为高危亚组和低危亚组。结果:除YTHDC2外,检测到的m6A RNA甲基化调节子在肿瘤组织中的表达与癌旁粘膜相比差异有统计学意义。其中,仅ALKBH5和METTL4在肿瘤中表达下调。两个亚组之间的基因分布不同。M6A RNA甲基化调节因子YTHDF1、HNRNPC、YTHDC2、YTHDC1、ZC3H13和RBM15在两组间的表达差异有统计学意义(P
Background: The RNA-seq FPKM data of 331 colorectal adenocarcinoma samples in The Cancer Genome Atlas database with matching clinical data were analyzed in order to reveal the prognostic value of m6A RNA methylation regulators in colon adenocarcinoma.Material/Methods: The expression of 13 m6A RNA methylated regulators in samples were analyzed. The samples were classified into Cluster I and II by consistent clustering. The gene distribution was analyzed by principal component analysis. Further functional analysis of selected m6A RNA genes was performed and potential risk characteristics was developed using Lasso Cox regression algorithm. Using minimum criteria, the risk coefficients of YTHDF1 and HNRNPC were detected for Cluster II. Patients were divided into high-risk and low-risk subgroups based on the risk characteristics. The clinical data were analyzed by univariate and multivariate Cox regression analysis.Results: Expression of the detected m6A RNA methylated regulators except YTHDC2 in tumors were significantly different from their adjacent mucosa. Among them, only ALKBH5 and METTL4 were downregulated in tumors. The gene distribution between the 2 subgroups were different. The expression of m6A RNA methylation regulators including YTHDF1, HNRNPC, YTHDC2, YTHDC1, ZC3H13, and RBM15 were different between the 2 groups (P