The prognostic marker FLVCR2 associated with tumor progression and immune infiltration for acute myeloid leukemia.
The prognostic marker FLVCR2 associated with tumor progression and immune infiltration for acute myeloid leukemia.
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与急性髓系白血病肿瘤进展和免疫浸润相关的预后标志物FLVCR2
DOI：
10.3389/fcell.2022.978786
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发表时间：
2022
影响因子：
5.5
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中科院分区：
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急性髓系白血病（acute myeloid leukemia，AML）是成人最常见的造血系统恶性肿瘤之一。肿瘤微环境（TME）对AML的发生、复发和进展具有关键影响。猫白血病病毒亚群C细胞受体家族成员2（FLVCR2）基因属于转运蛋白成员的主要易化剂超家族，其主要参与转运小分子。尚未研究FLVCR 2在AML中TME中的潜在作用。为了阐明FLVCR2在AML中的表达和作用，我们分析了Gene Expression Omnibus和The Cancer Genome Atlas数据库，发现AML患者中FLVCR2 mRNA表达显著增加。此外，基于对基因表达谱交互分析数据库的分析，FLVCR 2上调预测AML患者的总体生存率令人沮丧。我们的验证分析显示，通过蛋白质印迹和qPCR测定，AML骨髓中FLVCR 2相对于健康对照显著上调。采用基因集富集分析法探讨FLVCR2在AML中的相关机制。我们发现FLVCR2的高表达与AML患者的免疫细胞浸润程度和免疫评分有关，表明FLVCR2可能通过免疫反应对AML的进展起着至关重要的作用。具体而言，使用CIBERSORT分析，FLVCR 2上调与活化的自然杀伤细胞、活化的记忆性CD4+ T细胞、活化的树突状细胞和CD8+ T细胞的免疫浸润程度呈负相关。体外研究表明，FLVCR2基因沉默抑制AML细胞生长，促进其凋亡。这项研究提供了FLVCR2对肿瘤免疫的影响的见解，表明它可能作为一个独立的预后生物标志物，并与AML中的免疫浸润有关。
Acute myeloid leukemia (AML) is one of the most common hematopoietic malignancies in adults. The tumor microenvironment (TME) has a critical effect on AML occurrence, recurrence, and progression. The gene feline leukemia virus subgroup C cellular receptor family member 2 (FLVCR2) belongs to the major facilitator superfamily of transporter protein members, which is primarily involved in transporting small molecules. The potential role of FLVCR2 in the TME in AML has not been investigated. To clarify the expression and role of FLVCR2 in AML, we analyzed the Gene Expression Omnibus and The Cancer Genome Atlas databases and found that FLVCR2 mRNA expression significantly increased among patients with AML. Furthermore, based on an analysis of the Gene Expression Profiling Interactive Analysis database, FLVCR2 upregulation predicted dismal overall survival of patients with AML. Our validation analysis revealed the significant upregulation of FLVCR2 within the bone marrow of AML relative to healthy controls by western blotting and qPCR assays. Gene set enrichment analysis was conducted to explore FLVCR2’s related mechanism in AML. We found that high FLVCR2 expression was related to infiltration degrees of immune cells and immune scores among AML cases, indicating that FLVCR2 possibly had a crucial effect on AML progression through the immune response. Specifically, FLVCR2 upregulation was negatively related to the immune infiltration degrees of activated natural killer cells, activated memory CD4+ T cells, activated dendritic cells, and CD8+ T cells using CIBERSORT analysis. According to the in vitro research, FLVCR2 silencing suppressed AML cell growth and promoted their apoptosis. This study provides insights into FLVCR2’s effect on tumor immunity, indicating that it might serve as an independent prognostic biomarker and was related to immune infiltration within AML.