Department of Hematology, The First Hospital of Jiaxing, Jiaxing, Zhejiang 314000, P.R. China.
Int J Mol Med. 2018 Sep;42(3):1495-1507. doi: 10.3892/ijmm.2018.3739. Epub 2018 Jun 21.
Acute myeloid leukemia (AML) is the most common type of acute leukemia and is a heterogeneous clonal disorder. At present, the pathogenesis of AML and potential methods to effectively prevent AML have become areas of interest in research. In the present study, two messenger ribonucleic acid sequencing datasets of patients with AML were downloaded from the Cancer Genome Atlas and Gene Expression Omnibus databases. The differentially expressed genes (DEGs) of the poor and good prognosis groups were screened using the Linear Models for Microarray Data package, and the prognosis‑related genes were screened using univariate Cox regression analysis. A total of 206 significant DEGs were identified. Following univariate and multivariate Cox regression analysis, 14 genes significantly associated with prognosis were screened and six of these genes, including triggering receptor expressed on myeloid cells 2 (TREML2), cysteine‑glutamate transporter (SLC7A11), NACHT, LRR, and PYD domains‑containing protein 2 (NLRP2), DNA damage‑inducible transcript 4 protein (DDIT4), lymphocyte‑specific protein 1 (LSP1) and C‑type lectin domain family 11 member A (CLEC11A), were used to construct model equations for risk assessment. The prognostic scoring system was used to evaluate risk for each patient, and the results showed that patients in the low‑risk group had a longer survival time, compared with those in the high‑risk group (P=9.59e‑06 for the training dataset and P=0.00543 for the validation dataset). A total of eight main Kyoto Encyclopedia of Genes and Genomes pathways were identified, the top three of which were hematopoietic cell lineage, focal adhesion, and regulation of actin cytoskeleton. Taken together, the results showed that the scoring system established in the present study was credible and that the six genes were identified, which were significantly associated with the risk assessment of AML, offer potential as prognostic biomarkers. These findings may provide clues for further clarifying the pathogenesis of AML.
急性髓系白血病（AML）是最常见的急性白血病类型，是一种异质性克隆性疾病。目前，AML 的发病机制和潜在的有效预防 AML 的方法已成为研究的热点。本研究从癌症基因组图谱和基因表达综合数据库中下载了两份 AML 患者的信使核糖核酸测序数据集。使用线性模型微阵列数据分析包筛选不良和良好预后组的差异表达基因（DEG），使用单变量 Cox 回归分析筛选预后相关基因。共筛选出 206 个显著差异表达基因。经单变量和多变量 Cox 回归分析，筛选出 14 个与预后显著相关的基因，其中包括髓细胞表达的触发受体 2（TREML2）、胱氨酸-谷氨酸转运蛋白（SLC7A11）、NACHT、LRR 和 PYD 结构域包含蛋白 2（NLRP2）、DNA 损伤诱导转录 4 蛋白（DDIT4）、淋巴细胞特异性蛋白 1（LSP1）和 C 型凝集素结构域家族 11 成员 A（CLEC11A）。使用这些基因构建风险评估模型方程。采用预后评分系统对每位患者的风险进行评估，结果显示，低危组患者的生存时间较长，与高危组患者相比差异具有统计学意义（训练数据集 P=9.59e-06，验证数据集 P=0.00543）。共鉴定出 8 条主要京都基因与基因组百科全书通路，排名前 3 的通路分别为造血细胞谱系、焦点黏附和肌动蛋白细胞骨架调节。综上所述，本研究建立的评分系统具有可信度，筛选出与 AML 风险评估显著相关的 6 个基因，可为 AML 的预后标志物提供潜在的候选基因。这些发现可能为进一步阐明 AML 的发病机制提供线索。
