Identification of distinctive long noncoding RNA competitive interactions and a six-methylated-gene prognostic signature in acute myeloid leukemia with-5/del(5q) or-7/del(7q)
Identification of distinctive long noncoding RNA competitive interactions and a six-methylated-gene prognostic signature in acute myeloid leukemia with-5/del(5q) or-7/del(7q)
复制标题
鉴定急性髓系白血病中独特的长非编码 RNA 竞争性相互作用和六甲基化基因预后特征 -5/del(5q) 或-7/del(7q)
DOI：
10.1002/jcb.29391
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发表时间：
2020
影响因子：
4
通讯作者：
Hu Yu
中科院分区：
文献类型：
--
作者：
Yin Xuejiao;Huang Sui;Xu Aoshuang;Fan Fengjuan;Chen Lei;Sun Chunyan;Hu Yu
−5/del（5q）或−7/del（7q）的急性髓性白血病（AML）具有特殊的临床和生物学特征，但其分子机制和风险分层尚不清楚。方法从癌症基因组图谱（TCGA）中获取23例−5/del（5q）或−7/del（7q）患者和128例其他亚型急性髓系白血病患者的RNA测序和DNA甲基化。探讨了竞争性内源RNA （ceRNA）网络和DNA甲基化对基因表达的调控机制。为了找到这种AML亚型的可靠和特定的风险分层，通过四个独立的数据集建立了预后模型并进行了评估。结果鉴定出966个差异表达的长链非编码RNA、2274个差异表达基因和47个差异表达的microrna，并构建了ceRNA网络。对差异甲基化与差异表达基因进行综合分析后，19个基因的甲基化变异与基因表达呈相反趋势。建立了一个与总生存高度相关的六甲基化基因预后标记，并通过留一交叉验证法和排列试验验证了其性能。此外，该模型出色的预后价值得到了独立队列的支持，同时该模型的特异性通过三个独立数据集得到验证，表明它是一种高效的预测分类器，可将- 5/del（5q）或- 7/del（7q）与其他AML亚型区分开来。结论ceRNA网络可为−5/del（5q）或−7/del（7q）患者的诊断和治疗提供新的思路。对于- 5/del（5q）或- 7/del(7q) AML患者的预后，6‐甲基化基因预后标记是一个强大的、特异性的、临床实用的风险分层。
BackgroundAcute myeloid leukemia (AML) with −5/del(5q) or −7/del(7q) has special clinical and biological characteristics, but its molecular mechanisms and risk stratification remain unknown.MethodsThe RNA sequencing and DNA methylation of 23 patients with −5/del(5q) or −7/del(7q) and 128 patients with other subtypes of acute myeloid leukemia were obtained from The Cancer Genome Atlas (TCGA). The regulatory mechanisms of competitive endogenous RNA (ceRNA) network and DNA methylation on gene expression were explored. To find robust and specific risk stratification for this AML subtype, a prognostic model was established and evaluated through four independent data sets.ResultsWe identified 966 differentially expressed long noncoding RNA, 2274 differentially expressed genes, and 47 differentially expressed microRNAs, and constructed a ceRNA network. After the integrated analysis of differentially methylated and expressed genes, 19 genes showed the opposite trend between the methylation variation and gene expression. An six‐methylated‐gene prognostic signature which highly correlated with overall survival was established, and the performance was validated by leave‐one‐out cross validation method and permutation test. Furthermore, the excellent prognostic value of this model was supported by an independent cohort, while specificity of this model was validated by three independent data sets, suggesting it as a predictive classifier with high efficiency for distinguishing those with −5/del(5q) or −7/del(7q) from other AML subtypes.ConclusionsThe ceRNA network may provide new ideas for the diagnosis and treatment for patients with −5/del(5q) or −7/del(7q).The six‐methylated‐gene prognostic signature was a robust, specific, and clinically practical risk stratification for the outcome of patients with AML having −5/del(5q) or −7/del(7q).