Overexpression of HOXA10 is associated with unfavorable prognosis of acute myeloid leukemia
Overexpression of HOXA10 is associated with unfavorable prognosis of acute myeloid leukemia
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DOI：
10.1186/s12885-020-07088-6
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发表时间：
2020-06-22
期刊：
影响因子：
3.8
通讯作者：
Gao, Ya-yue
中科院分区：
文献类型：
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作者：
Guo, Chao;Ju, Qian-qian;Gao, Ya-yue
背景：HOXA家族基因是涉及细胞增殖和凋亡的关键转录因子。虽然很少有研究关注 HOXA10 在 AML 中的作用。我们的目的是研究 HOXA10 的预后意义。方法：我们从 GEO 和 BeatAML 数据库下载数据集，比较 AML 患者和对照之间的 HOXA 表达水平。 Kaplan-Meier 曲线用于估计 HOXA10 表达对 AML 生存的影响。使用R（版本3.6.0）获得HOXA10-high和-low组之间的差异表达基因、miRNA、lncRNA和甲基化区域。因此，使用 MSigDB 数据库完成基因集富集分析 (GSEA)。此外，还鉴定了 HOXA10 的调节 TF/microRNA/lncRNA。 LASSO-Cox 模型通过 glmnet 包将 OS 与临床和 HOXA10 相关的遗传变量进行拟合。结果：HOXA10 在 AML 患者中比对照组过度表达。 HOXA10 高组与较短的 OS 和 DFS 显着相关。总共有 1219 个 DEG、131 个 DEmiR、282 个 DElncR 被鉴定与 HOXA10 相关。 GSEA 显示 HOXA10 高组中有 12 个抑制通路和 3 个激活通路。此外，还建立了针对HOXA10的综合监管网络。 LASSO-Cox 模型将 OS 与 AML 生存风险评分进行拟合，其中包括年龄、种族、分子风险、IKZF2/LINC00649/LINC00839/FENDRR 和 has-miR-424-5p 的表达。时间依赖性 ROC 显示令人满意的 AUC（1 年 AUC 0.839、3 年 AUC 0.871 和 5 年 AUC 0.813）。结论：我们的研究确定 HOXA10 过度表达是 AML 的不良预后因素。 LASSOCOX 回归分析揭示了具有卓越诊断效用的新型 OS 预测模型。
Background: HOXA family genes were crucial transcription factors involving cell proliferation and apoptosis. While few studies have focused on HOXA10 in AML. We aimed to investigate the prognostic significance of HOXA10.Methods: We downloaded datasets from GEO and BeatAML database, to compare HOXA expression level between AML patients and controls. Kaplan-Meier curves were used to estimate the impact of HOXA10 expression on AML survival. The differentially expressed genes, miRNAs, lncRNAs and methylated regions between HOXA10-high and -low groups were obtained using R (version 3.6.0). Accordingly, the gene set enrichment analysis (GSEA) was accomplished using MSigDB database. Moreover, the regulatory TFs/microRNAs/lncRNAs of HOXA10 were identified. A LASSO-Cox model fitted OS to clinical and HOXA10-associated genetic variables by glmnet package.Results: HOXA10 was overexpressed in AML patients than that in controls. The HOXA10-high group is significantly associated with shorter OS and DFS. A total of 1219 DEGs, 131 DEmiRs, 282 DElncRs were identified to be associated with HOXA10. GSEA revealed that 12 suppressed and 3 activated pathways in HOXA10-high group. Furthermore, the integrated regulatory network targeting HOXA10 was established. The LASSO-Cox model fitted OS to AML-survival risk scores, which included age, race, molecular risk, expression of IKZF2/LINC00649/LINC00839/ FENDRR and has-miR-424-5p. The time dependent ROC indicated a satisfying AUC (1-year AUC 0.839, 3-year AUC 0.871 and 5-year AUC 0.813).Conclusions: Our study identified HOXA10 overexpression as an adverse prognostic factor for AML. The LASSOCOX regression analysis revealed novel prediction model of OS with superior diagnostic utility.