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. 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. 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). Our study identified HOXA10 overexpression as an adverse prognostic factor for AML. The LASSO-COX regression analysis revealed novel prediction model of OS with superior diagnostic utility.

中文翻译：

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HOXA10的过表达与急性髓细胞性白血病的预后不良有关。

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AML中的HOXA10。我们旨在调查HOXA10的预后意义。我们从GEO和BeatAML数据库下载了数据集，以比较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存活的影响。使用R（版本3.6.0）获得HOXA10高和低组之间差异表达的基因，miRNA，lncRNA和甲基化区域。因此，使用MSigDB数据库完成了基因集富集分析（GSEA）。此外，鉴定了HOXA10的调节性TF / microRNA / lncRNA。LASSO-Cox模型通过glmnet软件包将OS适应临床和HOXA10相关的遗传变量。AML患者中HOXA10的表达高于对照组。HOXA10高组明显与较短的OS和DFS相关。共鉴定出1219个DEG，131个DEmiR，282个DElncR与HOXA10相关。GSEA揭示高HOXA10组中有12条抑制途径和3条激活途径。此外，建立了针对HOXA10的集成监管网络。LASSO-Cox模型使OS适合AML生存风险评分，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表示令人满意的AUC（1年AUC 0.839、3年AUC 0.871和5年AUC 0.813）。我们的研究确定HOXA10过表达是AML的不良预后因素。LASSO-COX回归分析揭示了具有卓越诊断效用的新型OS预测模型。