Xie Kun-Ying, Wei Jin
Department of Hematology, Affiliated Hospital of North Sichuan Medical College, Nanchong, China.
Transl Cancer Res. 2024 Nov 30;13(11):5995-6003. doi: 10.21037/tcr-24-758. Epub 2024 Nov 12.
Acute myeloid leukemia (AML) is a highly heterogeneous hematological malignancy. The key problem lies in the complexity of the genome, so that drug resistance and relapse have become the main problems. Recent studies have found an association between synaptotagmin-like 4 (SYTL4) and drug resistance in triple-negative breast cancer and its high expression is correlated with poor prognosis; however, it is unclear whether this gene is associated with the prognosis of AML. This study aimed to investigate the role and action mechanism of SYTL4 in AML.
We downloaded gene expression profiles and corresponding clinical data from The Cancer Genome Atlas (TCGA) public database and conducted differential and survival analyses using the Limma and survival packages in R. The receiver operating characteristic (ROC) curve, univariate COX, and multivariate COX were used for gene prediction analysis. Co-expression analysis of SYTL4 was performed using Limma, and enrichment analysis of differentially expressed genes in the SYTL4 high- and low-expression groups was conducted. We performed immune cell infiltration using the CIBERSORTx algorithm.
The expression level of SYTL4 was highest in the poor prognosis group, and lowest in the good prognosis group. Survival was better in the SYTL4 low expression group than that in the high expression group. The areas under the ROC curve for TCGA-Acute Myeloid Leukemia (TCGA-LAML) at 1, 3, and 5 years were 0.725, 0.683, and 0.787, respectively. Sushi repeat protein X-linked 2 (SRPX2), caveolae associated protein 2 (CAVIN2), and other genes were identified as positive regulators of SYTL4 expression, whereas lactoperoxidase (LPO), diacylglycerol lipase beta (DAGLB), and other genes were identified as negative regulators. Differentially expressed genes in the SYTL4 high- and low-expression groups were enriched in pathways such as the embryonic skeletal system and platelet alpha granules. Differences were observed in follicular helper T cells, Tregs, monocytes, and M2 macrophages between SYTL4 high- and low-expression groups.
SYTL4 expression negatively correlates with AML prognosis and may be associated with exosome secretion in AML.
急性髓系白血病（AML）是一种高度异质性的血液系统恶性肿瘤。关键问题在于基因组的复杂性，致使耐药性和复发成为主要问题。近期研究发现，突触结合蛋白样4（SYTL4）与三阴性乳腺癌的耐药性相关，其高表达与预后不良相关；然而，该基因是否与AML的预后相关尚不清楚。本研究旨在探讨SYTL4在AML中的作用及作用机制。
我们从癌症基因组图谱（TCGA）公共数据库下载基因表达谱及相应临床数据，并使用R语言中的Limma和生存包进行差异分析和生存分析。采用受试者工作特征（ROC）曲线、单因素COX和多因素COX进行基因预测分析。使用Limma进行SYTL4的共表达分析，并对SYTL4高表达组和低表达组中的差异表达基因进行富集分析。我们使用CIBERSORTx算法进行免疫细胞浸润分析。
SYTL4的表达水平在预后不良组中最高，在预后良好组中最低。SYTL4低表达组的生存率高于高表达组。TCGA急性髓系白血病（TCGA-LAML）在1年、3年和5年时的ROC曲线下面积分别为0.725、0.683和0.787。寿司重复蛋白X连锁2（SRPX2）、小窝相关蛋白2（CAVIN2）等基因被鉴定为SYTL4表达的正调控因子，而乳过氧化物酶（LPO）、二酰甘油脂肪酶β（DAGLB）等基因被鉴定为负调控因子。SYTL4高表达组和低表达组中的差异表达基因在胚胎骨骼系统和血小板α颗粒等通路中富集。SYTL4高表达组和低表达组在滤泡辅助性T细胞、调节性T细胞、单核细胞和M2巨噬细胞方面存在差异。
SYTL4表达与AML预后呈负相关，可能与AML中的外泌体分泌有关。
