Hu Tingting, Zhang Yingjie, Yang Tianqing, He Qingnan, Zhao Mingyi
Department of Pediatrics, Third Xiangya Hospital, Central South University, Changsha, China.
College of Biology, Hunan University, Changsha, China.
Front Genet. 2022 Mar 11;13:795820. doi: 10.3389/fgene.2022.795820. eCollection 2022.
Acute myelogenous leukemia (AML) is nosocomial with the highest pediatric mortality rates and a relatively poor prognosis. () is a tumorigenic and high-glycosylated cell surface protein that has been proven to be linked with the carcinogenic effects in solid tumors, but no hematologic tumors have been reported. We focus on exploring the molecular mechanism of in the regulation of the occurrence and development of AML to provide a research basis for the screening of markers related to the treatment and prognosis. Datasets on RNA Sequencing (RNA-seq) and mRNA expression profiles of 510 samples were obtained from The Cancer Genome Atlas Program/The Genotype-Tissue Expression (Tcga-gtex) on 10 March 2021, which included the information on 173 AML tumorous tissue samples and 337 normal blood samples. The differential expression, identification of prognostic genes based on the COX regression model, and LASSO regression were analyzed. In order to better verify, experiments including gene knockdown mediated by small interfering RNA (siRNA), cell proliferation assays, and Western blot were prefomed. We studied the possible associated pathways through which may have an impact on the pathogenesis and prognosis of AML by gene set enrichment analysis (GSEA). A total of 11,490 differential expression genes (DEGs) were identified. Among them, 4,164 genes were upregulated, and 7,756 genes were downregulated. The univariate Cox regression analysis and LASSO regression analysis found that 28 genes including , , and other genes were associated with overall survival (OS). After multivariate Cox analysis, a total of 10 genes were considered significantly correlated with OS in AML including , which had a poor impact on AML ( <0.05). The experiment results also supported the above conclusion. We identified 25 pathways, including the E2F signaling pathway, signaling pathway, and signaling pathway, that were significantly upregulated in AML samples with high expression ( < 0.05) by GSEA. Further, the results of the experiment suggested that participates in the development of AML through the signaling pathway or/and signaling pathway. This study first proved that the expression of was elevated in AML, which was correlated with poor clinical characteristics and prognosis. In addition, participates in the development of AML through the signaling pathway.
急性髓系白血病（AML）是医院获得性疾病，具有最高的儿童死亡率且预后相对较差。（）是一种具有致瘤性且高度糖基化的细胞表面蛋白，已被证明与实体瘤的致癌作用有关，但尚未有血液系统肿瘤的相关报道。我们专注于探索（）在AML发生发展调控中的分子机制，为筛选与治疗和预后相关的标志物提供研究依据。2021年3月10日从癌症基因组图谱计划/基因型-组织表达数据库（Tcga-gtex）获得了510个样本的RNA测序（RNA-seq）和mRNA表达谱数据集，其中包括173个AML肿瘤组织样本和337个正常血液样本的信息。分析了差异表达、基于COX回归模型的预后基因鉴定以及LASSO回归。为了更好地验证，进行了包括小干扰RNA（siRNA）介导的基因敲低、细胞增殖测定和蛋白质印迹等实验。我们通过基因集富集分析（GSEA）研究了（）可能影响AML发病机制和预后的相关途径。共鉴定出11490个差异表达基因（DEG）。其中，4164个基因上调，7756个基因下调。单变量Cox回归分析和LASSO回归分析发现，包括（）、（）等在内的28个基因与总生存期（OS）相关。多变量Cox分析后，共有10个基因被认为与AML的OS显著相关，包括（），其对AML有不良影响（<0.05）。实验结果也支持上述结论。通过GSEA，我们在高（）表达的AML样本中鉴定出25条通路显著上调，包括E2F信号通路、（）信号通路和（）信号通路（<0.05）。此外，实验结果表明（）通过（）信号通路或/和（）信号通路参与AML的发展。本研究首次证明（）在AML中表达升高，这与不良的临床特征和预后相关。此外，（）通过（）信号通路参与AML的发展。
