Department of Hematology, The First Affiliated Hospital, Harbin Medical University, Harbin, China.
Department of Hematology, The Fourth Affiliated Hospital, Harbin Medical University, Harbin, China.
Mol Biol Rep. 2023 Oct;50(10):8445-8457. doi: 10.1007/s11033-023-08721-w. Epub 2023 Aug 26.
The overall survival (OS) rate of adult patients suffering from acute myeloid leukaemia (AML) remains unsatisfactory at less than 40%. Current risk stratification systems fail to provide accurate guidelines for precise treatment. Novel biomarkers for predicting prognosis are urgently needed. Plexin B2 (PLXNB2), a functional receptor of angiogenin (ANG), has been found to be aberrantly expressed in multitudinous tumours. We detected overexpression of PLXNB2 mRNA in AML via transcriptome microarray analysis. This study aims to explore the potential role of PLXNB2 as a biomarker of prognosis and a prospective target of AML.
qRT‒PCR was conducted to verify the expression of PLXNB2 mRNA in bone marrow mononuclear cells from AML patients. Immunohistochemical and immunofluorescence staining were performed and confirmed increased expression of PLXNB2 protein in AML bone marrow tissues. Data on PLXNB2 expression, prognosis and clinical features were accessed from multiple bioinformatic databases, including The Cancer Genome Atlas (TCGA). Genes coexpressed and correlated with PLXNB2 were identified and analysed in the TCGA AML cohort. Metascape was applied for functional and pathway enrichment analysis of genes related to PLXNB2. Small molecular agents and traditional Chinese medicines potentially targeting genes related to PLXNB2 were screened via the Connectivity Map, TCMSP and HIT databases.
PLXNB2 mRNA and protein levels are higher in AML samples than in normal controls. Overexpression of PLXNB2 is associated with worse OS in AML. Patients with high PLXNB2 expression might benefit more from haematopoietic stem cell transplantation (HSCT) (indicated by prolonged OS) than those with only chemotherapy treatment. Differentially expressed genes between the high and low PLXNB2 expression groups were overlapped with PLXNB2-coexpressed genes, and genes that overlapped were enriched in immune functions, endothelial cell regulation and cell interaction gene sets, indicating the potential function of PLXNB2 in AML. A total of 36 hub genes were identified from the differentially expressed genes, and MRC1, IL10, CD163 and CCL22 had significant prognostic value for AML. Analysis of the connectivity map and traditional agents revealed that honokiol, morphines, triptolide and paeoniflorin could be potential treatment regimens.
The overexpression of PLXNB2 is an adverse prognostic factor in adult AML patients and could be used as a potential biomarker. PLXNB2 might exert an oncogenic role by modulating immune functions, endothelial cell functions and cell interactions. AML patients with high PLXNB2 expression could benefit more from HSCT.
成人急性髓系白血病（AML）患者的总体生存率（OS）仍不理想，低于 40%。目前的风险分层系统无法为精确治疗提供准确的指导。迫切需要新的生物标志物来预测预后。黏附素（ANG）的功能性受体 Plexin B2（PLXNB2）已在多种肿瘤中发现表达异常。我们通过转录组微阵列分析检测到 AML 中 PLXNB2mRNA 的过表达。本研究旨在探讨 PLXNB2 作为预后生物标志物和 AML 潜在治疗靶点的作用。
qRT-PCR 检测 AML 患者骨髓单个核细胞中 PLXNB2mRNA 的表达。通过免疫组织化学和免疫荧光染色证实 AML 骨髓组织中 PLXNB2 蛋白表达增加。从多个生物信息学数据库（包括癌症基因组图谱（TCGA））获取 PLXNB2 表达、预后和临床特征数据。在 TCGA-AML 队列中鉴定并分析与 PLXNB2 共表达和相关的基因。Metascape 用于分析与 PLXNB2 相关基因的功能和通路富集。通过 Connectivity Map、TCMSP 和 HIT 数据库筛选潜在靶向与 PLXNB2 相关基因的小分子药物和中药。
PLXNB2mRNA 和蛋白在 AML 样本中的表达高于正常对照。PLXNB2 的过表达与 AML 患者的总生存期（OS）较差相关。高 PLXNB2 表达的患者可能从造血干细胞移植（HSCT）中获益更多（表现为 OS 延长），而仅接受化疗治疗的患者获益较少。高和低 PLXNB2 表达组之间差异表达的基因与 PLXNB2 共表达基因重叠，并且重叠基因富集在免疫功能、内皮细胞调节和细胞相互作用基因集，提示 PLXNB2 在 AML 中的潜在功能。从差异表达基因中鉴定出 36 个核心基因，MRC1、IL10、CD163 和 CCL22 对 AML 具有显著的预后价值。连接图谱和传统药物的分析表明，厚朴酚、吗啡、雷公藤内酯醇和芍药苷可能是潜在的治疗方案。
PLXNB2 的过表达是成人 AML 患者不良预后的一个因素，可作为潜在的生物标志物。PLXNB2 可能通过调节免疫功能、内皮细胞功能和细胞相互作用发挥致癌作用。高 PLXNB2 表达的 AML 患者可能从 HSCT 中获益更多。
