DataSheet1_LYPD3, a New Biomarker and Therapeutic Target for Acute Myelogenous Leukemia.PDF

Background: Acute myelogenous leukemia (AML) is nosocomial with the highest pediatric mortality rates and a relatively poor prognosis. C4.4A(LYPD3) 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 LYPD3 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.Methods: 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 LYPD3 may have an impact on the pathogenesis and prognosis of AML by gene set enrichment analysis (GSEA).Results: 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 LYPD3, DNAJC8, 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 LYPD3, which had a poor impact on AML (p

背景：急性髓系白血病（AML）作为一种医院内感染性疾病，具有最高的儿童死亡率以及相对较差的预后。C4.4A（LYPD3）是一种具有肿瘤生成性和高度糖基化的细胞表面蛋白，已被证实与实体肿瘤的致癌效应相关联，但尚未有关于造血肿瘤的报道。本研究旨在探究LYPD3在AML发生和发展过程中的分子调控机制，以期为相关治疗和预后标记物的筛选提供研究基础。方法：于2021年3月10日，从癌症基因组图谱计划/基因型-组织表达（Tcga-gtex）获取了510个样本的RNA测序（RNA-seq）和mRNA表达谱数据集，包括173个AML肿瘤组织样本和337个正常血液样本的信息。对差异表达进行了分析，并基于COX回归模型鉴定了预后基因，同时进行了LASSO回归分析。为了更好地验证，进行了包括由小干扰RNA（siRNA）介导的基因敲低、细胞增殖实验和Western blot等实验。通过基因集富集分析（GSEA）研究了LYPD3可能通过哪些途径影响AML的发病机制和预后。结果：共鉴定出11,490个差异表达基因（DEGs），其中4,164个基因表达上调，7,756个基因表达下调。单因素Cox回归分析和LASSO回归分析发现，包括LYPD3、DNAJC8等在内的28个基因与总生存期（OS）相关。在多因素Cox分析中，共考虑了10个与AML OS显著相关的基因，其中包括LYPD3，其对AML具有不良影响（p